Search

Your search keyword '"Pellet-Many C"' showing total 32 results
Start Over Author "Pellet-Many C"
32 results on '"Pellet-Many C"'

1. The role of the co-receptor neuropilin-1 in human vascular smooth muscle cells

Author

Pellet-Many, C. A. P.

Subjects
610
Abstract

Neuropilin-1 (NRP1) is a co-receptor required for neuronal and vascular development, which binds to class 3 semaphorins and VEGFs. NRP1 has been strongly implicated in VEGF-induced endothelial cell migration. VEGF has been shown to regulate vascular smooth muscle cell (VSMC) function in vitro. Evidence from mutant mice also suggests that NRP1 disruption in vivo can affect VSMC as well as endothelial function. I therefore investigated the role of NRPs in VSMC biological functions and more particularly in their migration. Western blotting showed that NRP1 and the related molecule, NRP2, were strongly expressed in human coronary artery SMC (HCASMC), whereas the major VEGF signalling receptor VEGFR2/KDR was not detectable. A high molecular weight NRP1-immunoreactive band (>250 kDa) was also strongly expressed in HCASMC, but was not detected either in cognate Human coronary artery endothelial cells (HCAEC) or in Human umbilical vein EC. The high molecular weight species was decreased significantly by treating the SMCs with chondroitinase, an enzyme that specifically chondroitin sulphate (CS) residues found in CS proteoglycan. Treatment with heparitinase, an enzymethat specifically heparan sulphate (HS) residues also resulted in a decrease of the highmolecular weight band but to a lesser extent than chondroitinase. Finally, treatment of SMC with both enzymes caused the complete disappearance of the high molecular weight species. Hence, in SMCs, in addition to the known NRP1 species at 130 kDa, NRP1 exists as a glycosaminoglycan containing either chondroitin sulphate or heparan sulphate polysaccharide chains. Mutational analysis of candidate O-linked glycosylation sites in the NRP1 extracellular domain showed that glycosylation occurred at serine 612. The importance of this gly-cosaminoglycan (GAG) modification was assessed by generating a construct of NRP1 lacking this GAG modification, called S612A. This was done by generation of an adenovirus NRP1 mutant with an alanine residue instead of the serine found in the wild-type species, however, the over-expression of the S612A NRP1 mutant in VSMC caused no signicant difference in PDGF-induced HCASMC migration. VEGF was able to bind significantly to ECs and SMCs but did not induce a significant migratory response of SMCs in contrast to PDGF-AA and PDGF-BB. PDGF-BB-induced HCASMC migration in transwell assays was inhibited by EG3287, a NRP1-specific antagonist, which blocks the ability of VEGF-A^1^6^5 to bind to NRP1. Furthermore, the migratory response to PDGF-BB was significantly decreased by siRNA-mediated knockdown of NRP1, NRP2 or a neuropilin interacting protein (NIP1 or synectin), and by pre-treatment with soluble NRP1 or NRP1 b1 domain (NRP1 VEGF binding domain). NRP1 knockdown also inhibited the migratory response to PDGF-AA. NRP1 was found to physically interact with PDGFR\alpha, but not with PDGFR\beta, as determined by co-immunoprecipitation. PDGFR\alpha, but not PDGFR\beta, phosphorylation was decreased in response to PDGF-AA and PDGF-BB when NRP1 was knocked down in HCASMC. Intracellular signalling in response to PDGF-BB stimulation was investigated in HCASMCs with NRP1 knockdown. PDGF-BB stimulated tyrosine phosphorylation of the adapter protein p130Cas, which has been stronlgy implicated in cellular and molecular processes involved in cell migration. NRP1 knockdown reduced p130Cas phosphorylation, but had little effect on signalling pathways, such as ERK1/2, Akt, cofilin, Hsp27 and FAK. To investigate the contribution of the NRP1 intracellular domain in PDGF-induced migration and signalling, I generated a NRP1 construct lacking the intracellular domain by introducing a stop codon after the transmembrane domain. Overexpression of NRP1 lacking its C-terminus in HCASMC resulted in a decrease of PDGF-induced migration and activation of phospho-p130Cas. Furthermore, p130Cas knockdown also inhibited PDGF- induced HCASMC migration, thus reinforcing the importance of p130Cas phosphorylation in NRP1-dependent cell migration. The findings that NRP1 is strongly expressed in HCASMC in a CS-GAG and a HS-GAG modified form and plays a role in the chemotactic response to PDGF-BB, highlight the possible involvement of NRPs in neotintima formation in vasculoproliferative diseases.

Published
2010

6. Poster session 1Cell growth, differentiation and stem cells - Heart72Understanding the metabolism of cardiac progenitor cells: a first step towards controlling their proliferation and differentiation?73Expression of pw1/peg3 identifies a new cardiac adult stem cell population involved in post-myocardial infarction remodeling74Long-term stimulation of iPS-derived cardiomyocytes using optogenetic techniques to promote phenotypic changes in E-C coupling75Benefits of electrical stimulation on differentiation and maturation of cardiomyocytes from human induced pluripotent stem cells76Constitutive beta-adrenoceptor-mediated cAMP production controls spontaneous automaticity of human induced pluripotent stem cell-derived cardiomyocytes77Formation and stability of T-tubules in cardiomyocytes78Identification of miRNAs promoting human cardiomyocyte proliferation by regulating Hippo pathway79A direct comparison of foetal to adult epicardial cell activation reveals distinct differences relevant for the post-injury response80Role of neuropilins in zebrafish heart regeneration81Highly efficient immunomagnetic purification of cardiomyocytes derived from human pluripotent stem cells82Cardiac progenitor cells posses a molecular circadian clock and display large 24-hour oscillations in proliferation and stress tolerance83Influence of sirolimus and everolimus on bone marrow-derived mesenchymal stem cell biology84Endoglin is important for epicardial behaviour following cardiac injuryCell death and apoptosis - Heart87Ultrastructural alterations reflecting Ca2+ handling and cell-to-cell coupling disorders precede occurrence of severe arrhythmias in intact animal heart88Urocortin-1 promotes cardioprotection through ERK1/2 and EPAC pathways: role in apoptosis and necrosis89Expression p38 MAPK and Cas-3 in myocardium LV of rats with experimental heart failure at melatonin and enalapril introductionTranscriptional control and RNA species - Heart92Accumulation of beta-amyloid 1-40 in HF patients: the role of lncRNA BACE1-AS93Role of miR-182 in zebrafish and mouse models of Holt-Oram syndrome94Mir-27 distinctly regulates muscle-enriched transcription factors and growth factors in cardiac and skeletal muscle cells95AF risk factors impair PITX2 expression leading to Wnt-microRNA-ion channel remodelingCytokines and cellular inflammation - Heart98Post-infarct survival depends on the interplay of monocytes, neutrophils and interferon gamma in a mouse model of myocardial Infarction99Inflammatory cd11b/c cells play a protective role in compensated cardiac hypertrophy by promoting an orai3-related pro-survival signal100Anti-inflammatory effects of endothelin receptor blockade in the atrial tissue of spontaneously hypertensive rats101Mesenchymal stromal cells reduce NLRP3 inflammasome activity in Coxsackievirus B3-induced myocarditis102Mesenchymal stromal cells modulate monocytes trafficking in Coxsackievirus B3-induced myocarditis103The impact of regulatory T lymphocytes on long-term mortality in patients with chronic heart failure104Temporal dynamics of dendritic cells after ST-elevation myocardial infarction relate with improvement of myocardial functionGrowth factors and neurohormones - Heart107Preconditioning of hypertrophied heart: miR-1 and IGF-1 crosstalk108Modulation of catecholamine secretion from human adrenal chromaffin cells by manipulation of G protein-coupled receptor kinase-2 activity109Evaluation of cyclic adenosin-3,5- monophosphate and neurohormones in patients with chronic heart failureNitric oxide and reactive oxygen species - Heart112Hydrogen sulfide donor inhibits oxidative and nitrosative stress, cardiohemodynamics disturbances and restores cNOS coupling in old rats113Role and mechanisms of action of aldehydes produced by monoamine oxidase A in cardiomyocyte death and heart failure114Exercise training has contrasting effects in myocardial infarction and pressure-overload due to different endothelial nitric oxide synthase regulation115S-Nitroso Human Serum Albumin dose-dependently leads to vasodilation and alters reactive hyperaemia in coronary arteries of an isolated mouse heart model116Modulating endothelial nitric oxide synthase with folic acid attenuates doxorubicin-induced cardiomyopathy119Effects of long-term very high intensity exercise on aortic structure and function in an animal model120Electron paramagnetic resonance spectroscopy quantification of nitrosylated hemoglobin (HbNO) as an index of vascular nitric oxide bioavailability in vivo121Deletion of repressor activator protein 1 impairs acetylcholine-induced relaxation due to production of reactive oxygen speciesExtracellular matrix and fibrosis - Heart124MicroRNA-19b is associated with myocardial collagen cross-linking in patients with severe aortic stenosis. Potential usefulness as a circulating biomarker125A new ex vivo model to study cardiac fibrosis126Heterogeneity of fibrosis and fibroblast differentiation in the left ventricle after myocardial infarction127Effect of carbohydrate metabolism degree compensation to the level of galectin-3 changes in hypertensive patients with chronic heart failure and type 2 diabetes mellitus128Statin paradox in association with calcification of bicuspid aortic valve interstitial cells129Cardiac function remains impaired despite reversible cardiac fibrosis after healed experimental viral myocarditisIon channels, ion exchangers and cellular electrophysiology - Heart132Identifying a novel role for PMCA1 (Atp2b1) in heart rhythm instability133Mutations of the caveolin-3 gene as a predisposing factor for cardiac arrhythmias134The human sinoatrial node action potential: time for a computational model135iPSC-derived cardiomyocytes as a model to dissect ion current alterations of genetic atrial fibrillation136Postextrasystolic potentiation in healthy and diseased hearts: effects of the site of origin and coupling interval of the preceding extrasystole137Absence of Nav1.8-based (late) sodium current in rabbit cardiomyocytes and human iPSC-CMs138hiPSC-derived cardiomyocytes from Brugada Syndrome patients without identified mutations do not exhibit cellular electrophysiological abnormalitiesMicrocirculation141Atherogenic indices, collagen type IV turnover and the development of microvascular complications- study in diabetics with arterial hypertension142Changes in the microvasculature and blood viscosity in women with rheumatoid arthritis, hypercholesterolemia and hypertensionAtherosclerosis145Shear stress regulates endothelial autophagy: consequences on endothelial senescence and atherogenesis146Obstructive sleep apnea causes aortic remodeling in a chronic murine model147Aortic perivascular adipose tissue displays an aged phenotype in early and late atherosclerosis in ApoE-/- mice148A systematic evaluation of the cellular innate immune response during the process of human atherosclerosis149Inhibition of Coagulation factor Xa increases plaque stability and attenuates the onset and progression of atherosclerotic plaque in apolipoprotein e-deficient mice150Regulatory CD4+ T cells from patients with atherosclerosis display pro-inflammatory skewing and enhanced suppression function151Hypoxia-inducible factor (HIF)-1alpha regulates macrophage energy metabolism by mediating miRNAs152Extracellular S100A4 is a key player of smooth muscle cell phenotypic transition: implications in atherosclerosis153Microparticles of healthy origins improve atherosclerosis-associated endothelial progenitor cell dysfunction via microRNA transfer154Arterial remodeling and metabolism impairment in early atherosclerosis155Role of pannexin1 in atherosclerotic plaque formationCalcium fluxes and excitation-contraction coupling158Amphiphysin II induces tubule formation in cardiac cells159Interleukin 1 beta regulation of connexin 43 in cardiac fibroblasts and the effects of adult cardiac myocyte:fibroblast co-culture on myocyte contraction160T-tubular electrical defects contribute to blunted beta-adrenergic response in heart failure161Beat-to-beat variability of intracellular Ca2+ dynamics of Purkinje cells in the infarct border zone of the mouse heart revealed by rapid-scanning confocal microscopy162The efficacy of late sodium current blockers in hypertrophic cardiomyopathy is dependent on genotype: a study on transgenic mouse models with different mutations163Synthesis of cADPR and NAADP by intracellular CD38 in heart: role in inotropic and arrhythmogenic effects of beta-adrenoceptor signalingContractile apparatus166Towards an engineered heart tissue model of HCM using hiPSC expressing the ACTC E99K mutation167Diastolic mechanical load delays structural and functional deterioration of ultrathin adult heart slices in culture168Structural investigation of the cardiac troponin complex by molecular dynamics169Exercise training restores myocardial and oxidative skeletal muscle function from myocardial infarction heart failure ratsOxygen sensing, ischaemia and reperfusion172A novel antibody specific to full-length stromal derived factor-1 alpha reveals that remote conditioning induces its cleavage by endothelial dipeptidyl peptidase 4173Attenuation of myocardial and vascular arginase activity by vagal nerve stimulation via a mechanism involving alpha-7 nicotinic receptor during cardiac ischemia and reperfusion174Novel nanoparticle-mediated medicine for myocardial ischemia-reperfusion injury simultaneously targeting mitochondrial injury and myocardial inflammation175Acetylcholine plays a key role in myocardial ischaemic preconditioning via recruitment of intrinsic cardiac ganglia176The role of nitric oxide and VEGFR-2 signaling in post ischemic revascularization and muscle recovery in aged hypercholesterolemic mice177Efficacy of ischemic preconditioning to protect the human myocardium: the role of clinical conditions and treatmentsCardiomyopathies and fibrosis180Plakophilin-2 haploinsufficiency leads to impaired canonical Wnt signaling in ARVC patient181Improved technique for customized, easier, safer and more reliable transverse aortic arch banding and debanding in mice as a model of pressure overload hypertrophy182Late sodium current inhibitors for the treatment of inducible obstruction and diastolic dysfunction in hypertrophic cardiomyopathy: a study on human myocardium183Angiotensin II receptor antagonist fimasartan has protective role of left ventricular fibrosis and remodeling in the rat ischemic heart184Role of High-Mobility Group Box 1 (HMGB1) redox state on cardiac fibroblasts activities and heart function after myocardial infarction185Atrial remodeling in hypertrophic cardiomyopathy: insights from mouse models carrying different mutations in cTnT186Electrophysiological abnormalities in ventricular cardiomyocytes from a Maine Coon cat with hypertrophic cardiomyopathy: effects of ranolazine187ZBTB17 is a novel cardiomyopathy candidate gene and regulates autophagy in the heart188Inhibition of SRSF4 in cardiomyocytes induces left ventricular hypertrophy189Molecular characterization of a novel cardiomyopathy related desmin frame shift mutation190Autonomic characterisation of electro-mechanical remodeling in an in-vitro leporine model of heart failure191Modulation of Ca2+-regulatory function by three novel mutations in TNNI3 associated with severe infant restrictive cardiomyopathyAging194The aging impact on cardiac mesenchymal like stromal cells (S+P+)195Reversal of premature aging markers after bariatric surgery196Sex-associated differences in vascular remodeling during aging: role of renin-angiotensin system197Role of the receptor for advanced glycation end-products (RAGE) in age dependent left ventricle dysfunctionsGenetics and epigenetics200hsa-miR-21-5p as a key factor in aortic remodeling during aneurysm formation201Co-inheritance of mutations associated with arrhythmogenic and hypertrophic cardiomyopathy in two Italian families202Lamin a/c hot spot codon 190: form various amino acid substitutions to clinical effects203Treatment with aspirin and atorvastatin attenuate cardiac injury induced by rat chest irradiation: Implication of myocardial miR-1, miR-21, connexin-43 and PKCGenomics, proteomics, metabolomics, lipidomics and glycomics206Differential phosphorylation of desmin at serines 27 and 31 drives the accumulation of preamyloid oligomers in heart failure207Potential role of kinase Akt2 in the reduced recovery of type 2 diabetic hearts subjected to ischemia / reperfusion injury208A proteomics comparison of extracellular matrix remodelling in porcine coronary arteries upon stent implantationMetabolism, diabetes mellitus and obesity211Targeting grk2 as therapeutic strategy for cancer associated to diabetes212Effects of salbutamol on large arterial stiffness in patients with metabolic syndrome213Circulating microRNA-1 and microRNA-133a: potential biomarkers of myocardial steatosis in type 2 diabetes mellitus214Anti-inflammatory nutrigenomic effects of hydroxytyrosol in human adipocytes - protective mechanisms of mediterranean diets in obesity-related inflammation215Alterations in the metal content of different cardiac regions within a rat model of diabetic cardiomyopathyTissue engineering218A novel conductive patch for application in cardiac tissue engineering219Establishment of a simplified and improved workflow from neonatal heart dissociation to cardiomyocyte purification and characterization220Effects of flexible substrate on cardiomyocytes cell culture221Mechanical stretching on cardiac adipose progenitors upregulates sarcomere-related genes

Author

Andre, E, primary, Yaniz-Galende, E, primary, Hamilton, C, primary, Dusting, G J, primary, Hellen, N, primary, Poulet, CE, primary, Diez Cunado, M, primary, Smits, AM, primary, Lowe, V, primary, Eckardt, D, primary, Du Pre, B, primary, Sanz Ruiz, R, primary, Moerkamp, A T, primary, Tribulova, N, primary, Smani, T, primary, Liskova, Y V, primary, Greco, S, primary, Guzzolino, E, primary, Franco, D, primary, Lozano-Velasco, E, primary, Knorr, M, primary, Pavoine, C, primary, Bukowska, A, primary, Van Linthout, S, primary, Miteva, K, primary, Sulzgruber, P, primary, Latet, S C, primary, Portnychenko, A, primary, Cannavo, A, primary, Kamilova, U, primary, Sagach, VF, primary, Santin, Y, primary, Octavia, Y, primary, Haller, PM, primary, Rubies, C, primary, Dei Zotti, F, primary, Wong, KHK, primary, Gonzalez Miqueo, A, primary, Kruithof, BPT, primary, Kadur Nagaraju, C, primary, Shaposhnikova, Y, primary, Songia, P, primary, Lindner, D, primary, Wilson, C, primary, Benzoni, P, primary, Fabbri, A, primary, Campostrini, G, primary, Jorge, E, primary, Casini, S, primary, Mengarelli, I, primary, Nikolov, A, primary, Bublikov, DS, primary, Kheloufi, M, primary, Walker, R E, primary, Van Dijk, RA, primary, Posthuma, JJ, primary, Dumitriu, I E, primary, Karshovska, E, primary, Sakic, A, primary, Alexandru, N, primary, Martin-Lorenzo, M, primary, Molica, F, primary, Taylor, RF, primary, Mcarthur, L, primary, Crocini, C, primary, Matsuyama, T-A, primary, Mazzoni, L, primary, Lin, W K, primary, Owen, TJ, primary, Scigliano, M, primary, Sheehan, A, primary, Bezerra Gurgel, A R, primary, Bromage, DI, primary, Kiss, A, primary, Ikeda, G, primary, Pickard, J M J, primary, Wirth, G, primary, Casos, K, primary, Khudiakov, A, primary, Nistal, JF, primary, Ferrantini, C, primary, Park, S-J, primary, Di Maggio, S, primary, Gentile, F, primary, Dini, L, primary, Buyandelger, B, primary, Larrasa-Alonso, J, primary, Schirmer, I, primary, Chin, SH, primary, Cimiotti, D, primary, Martini, H, primary, Hohensinner, P J, primary, Garabito, M, primary, Zeni, F, primary, Licholai, S, primary, De Bortoli, M, primary, Sivitskaya, L, primary, Viczenczova, C, primary, Rainer, PP, primary, Smith, LE, primary, Suna, G, primary, Gambardella, J, primary, Cozma, A, primary, De Gonzalo Calvo, D, primary, Scoditti, E, primary, Clark, B J, primary, Mansfield, C, primary, Gomez, L, primary, Llucia-Valldeperas, A, primary, De Pauw, A, additional, Porporato, P, additional, Bouzin, C, additional, Draoui, N, additional, Sonveaux, P, additional, Balligand, J-L, additional, Mougenot, N, additional, Formicola, L, additional, Nadaud, S, additional, Dierick, F, additional, Hajjar, RJ, additional, Marazzi, G, additional, Sassoon, D, additional, Hulot, J-S, additional, Zamora, VR, additional, Burton, FL, additional, Macquaide, N, additional, Smith, GL, additional, Hernandez, D, additional, Sivakumaran, P, additional, Millard, R, additional, Wong, RCB, additional, Pebay, A, additional, Shepherd, RK, additional, Lim, SY, additional, Owen, T, additional, Jabbour, RJ, additional, Kloc, M, additional, Kodagoda, T, additional, Denning, C, additional, Harding, SE, additional, Ramos, S, additional, Terracciano, C, additional, Gorelik, J, additional, Wei, K, additional, Bushway, P, additional, Ruiz-Lozano, P, additional, Mercola, M, additional, Moerkamp, AT, additional, Vegh, AMD, additional, Dronkers, E, additional, Lodder, K, additional, Van Herwaarden, T, additional, Goumans, MJ, additional, Pellet-Many, C, additional, Zachary, I, additional, Noack, K, additional, Bosio, A, additional, Feyen, DAM, additional, Demkes, EJ, additional, Dierickx, PJ, additional, Doevendans, PA, additional, Vos, MA, additional, Van Veen, AAB, additional, Van Laake, LW, additional, Fernandez Santos, ME, additional, Suarez Sancho, S, additional, Fuentes Arroyo, L, additional, Plasencia Martin, V, additional, Velasco Sevillano, P, additional, Casado Plasencia, A, additional, Climent, AM, additional, Guillem, M, additional, Atienza Fernandez, F, additional, Fernandez-Aviles, F, additional, Dingenouts, CKE, additional, Kruithof, BPT, additional, Smits, AM, additional, Knezl, V, additional, Szeiffova Bacova, B, additional, Egan Benova, T, additional, Viczenczova, C, additional, Goncalvesova, E, additional, Slezak, J, additional, Calderon-Sanchez, E, additional, Diaz, I, additional, Ordonez, A, additional, Salikova, S P, additional, Zaccagnini, G, additional, Voellenkle, C, additional, Sadeghi, I, additional, Maimone, B, additional, Castelvecchio, S, additional, Gaetano, C, additional, Menicanti, L, additional, Martelli, F, additional, Hatcher, C, additional, D'aurizio, R, additional, Groth, M, additional, Baugmart, M, additional, Mercatanti, A, additional, Russo, F, additional, Mariani, L, additional, Magliaro, C, additional, Pitto, L, additional, Lozano-Velasco, E, additional, Jodar-Garcia, A, additional, Galiano-Torres, J, additional, Lopez-Navarrete, I, additional, Aranega, A, additional, Wagensteen, R, additional, Quesada, A, additional, Franco, D, additional, Finger, S, additional, Karbach, S, additional, Kossmann, S, additional, Muenzel, T, additional, Wenzel, P, additional, Keck, M, additional, Favier, S, additional, Fuand, A, additional, Atassi, F, additional, Barbier, C, additional, Lompre, AM, additional, Hulot, JS, additional, Nikonova, Y, additional, Pluteanu, F, additional, Kockskaemper, J, additional, Chilukoti, RK, additional, Wolke, C, additional, Lendeckel, U, additional, Gardemann, A, additional, Goette, A, additional, Miteva, K, additional, Pappritz, K, additional, Mueller, I, additional, El-Shafeey, M, additional, Ringe, J, additional, Tschoepe, C, additional, Van Linthout, S, additional, Koller, L, additional, Richter, B, additional, Blum, S, additional, Koprak, M, additional, Huelsmann, M, additional, Pacher, R, additional, Goliasch, G, additional, Wojta, J, additional, Niessner, A, additional, Van Herck, P L, additional, Claeys, M J, additional, Haine, S E, additional, Lenders, G D, additional, Miljoen, H P, additional, Segers, V F, additional, Vandendriescche, T R, additional, Hoymans, V Y, additional, Vrints, C J, additional, Lapikova-Bryhinska, T, additional, Gurianova, V, additional, Portnichenko, H, additional, Vasylenko, M, additional, Zapara, Y, additional, Portnichenko, V, additional, Liccardo, D, additional, Lymperopoulos, A, additional, Santangelo, M, additional, Leosco, D, additional, Koch, WJ, additional, Ferrara, N, additional, Rengo, G, additional, Alieva, T, additional, Rasulova, Z, additional, Masharipova, D, additional, Dorofeyeva, N A, additional, Drachuk, KO, additional, Sicard, P, additional, Yucel, Y, additional, Dutaur, M, additional, Vindis, C, additional, Parini, A, additional, Mialet-Perez, J, additional, Van Deel, ED, additional, De Boer, M, additional, De Waard, MC, additional, Duncker, DJ, additional, Nagel, F, additional, Inci, M, additional, Santer, D, additional, Hallstroem, S, additional, Podesser, BK, additional, Kararigas, G, additional, Kietadisorn, R, additional, Swinnen, M, additional, Duimel, H, additional, Verheyen, F, additional, Chrifi, I, additional, Brandt, MM, additional, Cheng, C, additional, Janssens, S, additional, Moens, AL, additional, Batlle, M, additional, Dantas, AP, additional, Sanz, M, additional, Sitges, M, additional, Mont, L, additional, Guasch, E, additional, Lobysheva, I, additional, Beauloye, C, additional, Vanhoutte, PM, additional, Tang, EHC, additional, Beaumont, J, additional, Lopez, B, additional, Ravassa, S, additional, Hermida, N, additional, Valencia, F, additional, Gomez-Doblas, JJ, additional, San Jose, G, additional, De Teresa, E, additional, Diez, J, additional, Van De Merbel, AF, additional, Kruithof-De Julio, M, additional, Claus, P, additional, Dries, E, additional, Angelo Singh, A, additional, Vermeulen, K, additional, Roderick, HL, additional, Sipido, KR, additional, Driesen, RB, additional, Ilchenko, I, additional, Bobronnikova, L, additional, Myasoedova, V, additional, Alamanni, F, additional, Tremoli, E, additional, Poggio, P, additional, Becher, PM, additional, Gotzhein, F, additional, Klingel, K, additional, Blankenberg, S, additional, Westermann, D, additional, Zi, M, additional, Cartwright, E, additional, Campostrini, G, additional, Bonzanni, M, additional, Milanesi, R, additional, Bucchi, A, additional, Baruscotti, M, additional, Difrancesco, D, additional, Barbuti, A, additional, Fantini, M, additional, Wilders, R, additional, Severi, S, additional, Benzoni, P, additional, Dell' Era, P, additional, Serzanti, M, additional, Olesen, MS, additional, Muneretto, C, additional, Bisleri, G, additional, Amoros-Figueras, G, additional, Raga, S, additional, Campos, B, additional, Alonso-Martin, C, additional, Rodriguez-Font, E, additional, Vinolas, X, additional, Cinca, J, additional, Guerra, JM, additional, Mengarelli, I, additional, Schumacher, CA, additional, Veldkamp, MW, additional, Verkerk, AO, additional, Remme, CA, additional, Veerman, C, additional, Guan, K, additional, Stauske, M, additional, Tan, H, additional, Barc, J, additional, Wilde, A, additional, Verkerk, A, additional, Bezzina, C, additional, Tsinlikov, I, additional, Tsinlikova, I, additional, Nicoloff, G, additional, Blazhev, A, additional, Garev, A, additional, Andrienko, AV, additional, Lychev, VG, additional, Vorobova, EN, additional, Anchugina, DA, additional, Vion, AC, additional, Hammoutene, A, additional, Poisson, J, additional, Dupont, N, additional, Souyri, M, additional, Tedgui, A, additional, Codogno, P, additional, Boulanger, CM, additional, Rautou, PE, additional, Torres, M, additional, Montserrat, JM, additional, Almendros, I, additional, Austin, C A, additional, Holt, C M, additional, Rijs, K, additional, Wezel, A, additional, Hamming, JF, additional, Kolodgie, FD, additional, Virmani, R, additional, Schaapherder, AF, additional, Lindeman, JHN, additional, Posma, JJN, additional, Van Oerle, R, additional, Spronk, HMH, additional, Ten Cate, H, additional, Dinkla, S, additional, Kaski, JC, additional, Schober, A, additional, Chaabane, C, additional, Ambartsumian, N, additional, Grigorian, M, additional, Bochaton-Piallat, ML, additional, Dragan, E, additional, Andrei, E, additional, Niculescu, L, additional, Georgescu, A, additional, Gonzalez-Calero, L, additional, Maroto, AS, additional, Martinez, PJ, additional, Heredero, A, additional, Aldamiz-Echevarria, G, additional, Vivanco, F, additional, Alvarez-Llamas, G, additional, Meens, MJ, additional, Pelli, G, additional, Foglia, B, additional, Scemes, E, additional, Kwak, BR, additional, Caldwell, JL, additional, Eisner, DA, additional, Dibb, KM, additional, Trafford, AW, additional, Chilton, L, additional, Smith, G L, additional, Nicklin, S A, additional, Coppini, R, additional, Ferrantini, C, additional, Yan, P, additional, Loew, LM, additional, Poggesi, C, additional, Cerbai, E, additional, Pavone, F S, additional, Sacconi, L, additional, Tanaka, H, additional, Ishibashi-Ueda, H, additional, Takamatsu, T, additional, Gentile, F, additional, Pioner, JM, additional, Santini, L, additional, Sartiani, L, additional, Bargelli, V, additional, Mugelli, A, additional, Maciejewska, M, additional, Bolton, E L, additional, Wang, Y, additional, O'brien, F, additional, Ruas, M, additional, Lei, M, additional, Sitsapesan, R, additional, Galione, A, additional, Terrar, D A, additional, Smith, JG, additional, Garcia, D, additional, Barriales-Villa, R, additional, Monserrat, L, additional, Marston, SB, additional, Watson, S, additional, Tkach, S, additional, Faggian, G, additional, Terracciano, C M, additional, Perbellini, F, additional, Eiros Zamora, J, additional, Papadaki, M, additional, Messer, A, additional, Marston, S, additional, Gould, I, additional, Johnston, A, additional, Dunne, M, additional, Smith, G, additional, Kemi, OJ, additional, Pillai, M, additional, Davidson, SM, additional, Yellon, DM, additional, Tratsiakovich, Y, additional, Jang, J, additional, Gonon, AT, additional, Pernow, J, additional, Matoba, T, additional, Koga, J, additional, Egashira, K, additional, Burke, N, additional, Korpisalo, P, additional, Hakkarainen, H, additional, Laidinen, S, additional, Yla-Herttuala, S, additional, Ferrer-Curriu, G, additional, Perez, M, additional, Permanyer, E, additional, Blasco-Lucas, A, additional, Gracia, JM, additional, Castro, MA, additional, Barquinero, J, additional, Galinanes, M, additional, Kostina, D, additional, Kostareva, A, additional, Malashicheva, A, additional, Merino, D, additional, Ruiz, L, additional, Gomez, J, additional, Juarez, C, additional, Gil, A, additional, Garcia, R, additional, Hurle, MA, additional, Mazzoni, L, additional, Rossi, A, additional, Tesi, C, additional, Belardinelli, L, additional, Olivotto, I, additional, Eun-Ji, EJ, additional, Lim, B-K, additional, Choi, D-J, additional, Milano, G, additional, Bertolotti, M, additional, De Marchis, F, additional, Zollo, F, additional, Sommariva, E, additional, Capogrossi, M C, additional, Pompilio, G, additional, Bianchi, M E, additional, Raucci, A, additional, Scellini, B, additional, Tardiff, J, additional, Diolaiuti, L, additional, Ferrari, P, additional, Mansfield, C, additional, Luther, P, additional, Knoell, R, additional, Villalba, M, additional, Sanchez-Cabo, F, additional, Lopez-Olaneta, MM, additional, Ortiz-Sanchez, P, additional, Garcia-Pavia, P, additional, Lara-Pezzi, E, additional, Klauke, B, additional, Gerdes, D, additional, Schulz, U, additional, Gummert, J, additional, Milting, H, additional, Wake, E, additional, Kocsis-Fodor, G, additional, Brack, KE, additional, Ng, GA, additional, Smolina, N, additional, Majchrzak, M, additional, Moehner, D, additional, Wies, A, additional, Stehle, R, additional, Pfitzer, G, additional, Muegge, A, additional, Jaquet, K, additional, Maggiorani, D, additional, Lefevre, L, additional, Cussac, D, additional, Douin-Echinard, V, additional, Ebenbauer, B, additional, Kaun, C, additional, Prager, M, additional, Rega-Kaun, G, additional, Costa, G, additional, Onetti, Y, additional, Jimenez-Altayo, F, additional, Vila, E, additional, Dantas, A P, additional, Scopece, A, additional, Piacentini, L, additional, Bianchi, ME, additional, Capogrossi, MC, additional, Colombo, G, additional, Blaz, M, additional, Kapelak, B, additional, Sanak, M, additional, Bauce, B, additional, Calore, C, additional, Lorenzon, A, additional, Calore, M, additional, Poloni, G, additional, Mazzotti, E, additional, Rigato, I, additional, Daliento, L, additional, Basso, C, additional, Thiene, G, additional, Melacini, P, additional, Corrado, D, additional, Rampazzo, A, additional, Danilenko, NG, additional, Vaikhanskaya, TG, additional, Davydenko, OG, additional, Kura, B, additional, Yin, CH, additional, Kukreja, R, additional, Tribulova, N, additional, Lee, DI, additional, Sorge, M, additional, Glabe, C, additional, Paolocci, N, additional, Guarnieri, C, additional, Tomaselli, GF, additional, Kass, DA, additional, Van Eyk, JE, additional, Agnetti, G, additional, Cordwell, SJ, additional, White, MY, additional, Wojakowski, W, additional, Lynch, M, additional, Barallobre-Barreiro, J, additional, Yin, X, additional, Mayr, U, additional, White, S, additional, Jahingiri, M, additional, Hill, J, additional, Mayr, M, additional, Sorriento, D, additional, Ciccarelli, M, additional, Fiordelisi, A, additional, Campiglia, P, additional, Trimarco, B, additional, Iaccarino, G, additional, Sitar Taut, AV, additional, Schiau, S, additional, Orasan, O, additional, Halloumi, W, additional, Negrean, V, additional, Zdrenghea, D, additional, Pop, D, additional, Van Der Meer, RW, additional, Rijzewijk, LJ, additional, Smit, JWA, additional, Revuelta-Lopez, E, additional, Nasarre, L, additional, Escola-Gil, JC, additional, Lamb, HJ, additional, Llorente-Cortes, V, additional, Pellegrino, M, additional, Massaro, M, additional, Carluccio, MA, additional, Calabriso, N, additional, Wabitsch, M, additional, Storelli, C, additional, De Caterina, R, additional, Church, S J, additional, Callagy, S, additional, Begley, P, additional, Kureishy, N, additional, Mcharg, S, additional, Bishop, P N, additional, Unwin, R D, additional, Cooper, G J S, additional, Mawad, D, additional, Tonkin, J, additional, Bello, S O, additional, Simonotto, J D, additional, Lyon, A R, additional, Stevens, M M, additional, Harding, S E, additional, Kernbach, M, additional, Czichowski, V, additional, Fuentes, L, additional, Hernandez-Redondo, I, additional, Guillem, MS, additional, Fernandez, ME, additional, Sanz, R, additional, Atienza, F, additional, Soler-Botija, C, additional, Prat-Vidal, C, additional, Galvez-Monton, C, additional, Roura, S, additional, Perea-Gil, I, additional, Bragos, R, additional, and Bayes-Genis, A, additional

Published
2016
Full Text
View/download PDF

7. Poster session 2Morphogenetic mechanisms290MiR-133 regulates retinoic acid pathway during early cardiac chamber specification291Bmp2 regulates atrial differentiation through miR-130 during early heart looping formationDevelopmental genetics294Association of deletion allele of insertion/deletion polymorphism in alpha 2B adrenoceptor gene and hypertension with or without type 2 diabetes mellitus295Association of G1359A polymorphism of the endocannabinoid type 1 receptor (CNR1) with coronary artery disease (CAD) with type 2 diabetes mellitusCell growth, differentiation and stem cells - Vascular298Gamma-secretase inhibitor prevents proliferation and migration of ductus arteriosus smooth muscle cells: a role of Notch signaling in postnatal closure of ductus arteriosus299Mesenchymal stromal-like cells (MLCs) derived from induced pluripotent stem (iPS) cells: a promising therapeutic option to promote neovascularization300Sonic Hedgehog promotes mesenchymal stem cell differentiation to vascular smooth muscle cells in cardiovacsular disease301Proinflammatory cytokine secretion and epigenetic modification in endothelial cells treated LPS-GinfivalisCell death and apoptosis - Vascular304Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipidsTranscriptional control and RNA species - Vascular307MicroRNA-34a role in vascular calcification308Local delivery of a miR-146a inhibitor utilizing a clinically applicable approach attenuates neointima formation after vascular injury309Long noncoding RNA landscape of hypoxic endothelial cells310Specific circulating microRNAs levels associate with hypertension, hyperglycemia and dysfunctional HDL in acute coronary syndrome patientsCytokines and cellular inflammation - Vascular313Phosphodiesterase5A up-regulation in vascular endothelium under pro-inflammatory conditions: a newly disclosed anti-inflammatory activity for the omega-3polyunsaturated aatty acid docosahexaenoic acid314Cardiovascular risk modifying with extra-low dose anticytokine drugs in rhematoid arthritis315Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation316Lymphocytic myocarditis coincides with increased plaque inflammation and plaque hemorrhage in coronary arteries, facilitating myocardial infarction317Serum osteoprotegerin level predictsdeclined numerous of circulating endothelial- derived and mononuclear-derived progenitor cells in patients with metabolic syndromeGrowth factors and neurohormones - Vascular320Effect of gastrin-releasing peptide (GRP) on vascular inflammationSignal transduction - Heart323A new synthetic peptide regulates hypertrophy in vitro through means of the inhibition of nfkb324Inducible fibroblast-specific knockout of p38 alpha map kinase is cardioprotective in a mouse model of isoproterenol-induced cardiac hypertrophy325Regulation of beta-adrenoceptor-evoked inotropic responses by inhibitory G protein, adenylyl cyclase isoforms 5 and 6 and phosphodiesterases326Binding to RGS3 and stimulation of M2 muscarinic acetylcholine receptors modulates the substrate specificity of p190RhoGAP in cardiac myocytes327Cardiac regulation of post-translational modifications, parylation and deacetylation in LMNA dilated cardiomyopathy mouse model328Beta-adrenergic regulation of the b56delta/pp2a holoenzyme in cardiac myocytes through b56delta phosphorylation at serine 573Nitric oxide and reactive oxygen species - Vascular331Oxidative stress-induced miR-200c disrupts the regulatory loop among SIRT1, FOXO1 and eNOS332Antioxidant therapy prevents oxidative stress-induced endothelial dysfunction and Enhances Wound Healing333Morphological and biochemical characterization of red blood cell in coronary artery diseaseCytoskeleton and mechanotransduction - Heart336Novel myosin activator, JSH compounds, increased myocardial contractility without chronotropic effect in ratsExtracellular matrix and fibrosis - Vascular339Ablation of Toll-like receptor 9 causes cardiac rupture after myocardial infarction by attenuating proliferation and differentiation of cardiac fibroblasts340Altered vascular remodeling in the mouse hind limb ischemia model in Factor VII activating protease (FSAP) deficiencyVasculogenesis, angiogenesis and arteriogenesis343Pro-angiogenic effects of proly-hydroxylase inhibitors and their potential for use in a novel strategy of therapeutic angiogenesis for coronary total occlusion344Nrf2 drives angiogenesis in transcription-independent manner: new function of the master regulator of oxidative stress response345Angiogenic gene therapy, despite efficient vascular growth, is not able to improve muscle function in normoxic or chronically ischemic rabbit hindlimbs -role of capillary arterialization and shunting346Effect of PAR-1 inhibition on collateral vessel growth in the murine hind limb model347Quaking is a key regulator of endothelial cell differentiation, neovascularization and angiogenesis348"Emerging angiogenesis" in the chick chorioallantoic membrane (CAM). An in vivo study349Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis in vitro and in vivo via EMMPRINEndothelium352Reciprocal regulation of GRK2 and bradykinin receptor stimulation modulate Ca2+ intracellular level in endothelial cells353The roles of bone morphogenetic proteins 9 and 10 in endothelial inflammation and atherosclerosis354The contribution of GPR55 to the L-alpha-lysophosphatidylinositol-induced vasorelaxation in isolated human pulmonary arteries355The endothelial protective ACE inhibitor Zofenoprilat exerts anti-inflammatory activities through H2S production356A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction357Endothelial progenitor cells to apoptotic endothelial cell-derived microparticles ration differentiatesas preserved from reduced ejection fractionheart failure358Proosteogenic genes are activated in endothelial cells of patients with thoracic aortic aneurysm359Endothelin ETB receptors mediate relaxing responses to insulin in pericardial resistance arteries from patients with cardiovascular disease (CVD)Smooth muscle and pericytes362CX3CR1 positive myeloid cells regulate vascular smooth muscle tone by inducing calcium oscillations via activation of IP3 receptors363A novel function of PI3Kg on cAMP regulation, role in arterial wall hyperplasia through modulation of smooth muscle cells proliferation364NRP1 and NRP2 play important roles in the development of neointimal hyperplasia in vivo365Azithromycin induces autophagy in aortic smooth muscle cellsCoagulation, thrombosis and platelets368The real time in vivo evaluation of platelet-dependent aldosterone prothrombotic action in mice369Development of a method for in vivo detection of active thrombi in mice370The antiplatelet effects of structural analogs of the taurine chloramine371The influence of heparin anticoagulant drugs on functional state of human platelets372Regulation of platelet aggregation and adenosine diphosphate release by d dimer in acute coronary syndrome (in vitro study)Oxygen sensing, ischaemia and reperfusion375Sirtuin 5 mediates brain injury in a mouse model of cerebral ischemia-reperfusion376Abscisic acid: a new player in cardiomyocyte protection from ischaemia?377Protective effects of ultramicronized palmitoylethanolamide (PEA-um) in myocardial ischaemia and reperfusion injury in vivo378Identification of stem cell-derived cardiomyocytes using cardiac specific markers and additional testing of these cells in simulated ischemia/reperfusion system379Single-dose intravenous metformin treatment could afford significant protection of the injured rat kidney in an experimental model of ischemia-reperfusion380Cardiotoxicity of long acting muscarinic receptor antagonists used for chronic obstructive pulmonary disease381Dependence antioxidant potential on the concentration of amino acids382The impact of ischemia-reperfusion on physiological parameters,apoptosis and ultrastructure of rabbit myocardium with experimental aterosclerosisMitochondria and energetics385MicroRNA-1 dependent regulation of mitochondrial calcium uniporter (MCU) in normal and hypertrophied hearts386Mitochondrial homeostasis and cardioprotection: common targets for desmin and aB-crystallin387Overexpression of mitofusin-2 (Mfn2) and associated mitochondrial dysfunction in the diabetic heart388NO-dependent prevention of permeability transition pore (MPTP) opening by H2S and its regulation of Ca2+ accumulation in rat heart mitochondria389G protein coupled receptor kinase 2 (GRK2) is fundamental in recovering mitochondrial morphology and function after exposure to ionizing radiation (IR)Gender issues392Sex differences in pulmonary vascular control; focus on the nitric oxide pathwayAging395Heart failure with preserved ejection fraction develops when feeding western diet to senescence-accelerated mice396Cardiovascular markers as predictors of cognitive decline in elderly hypertensive patients397Changes in connexin43 in old rats with volume overload chronic heart failureGenetics and epigenetics400Calcium content in the aortic valve is associated with 1G>2G matrix metalloproteinase 1 polymorphism401Neuropeptide receptor gene s (NPSR1) polymorphism and sleep disturbances402Endothelin-1 gene Lys198Asn polymorphism in men with essential hypertension complicated and uncomplicated with chronic heart failure403Association of common polymorphisms of the lipoprotein lipase and pon1 genes with the metabolic syndrome in a sample of community participantsGenomics, proteomics, metabolomics, lipidomics and glycomics405Gene expression quantification using multiplexed color-coded probe pairs to determine RNA content in sporadic cardiac myxoma406Large-scale phosphorylation study of the type 2 diabetic heart subjected to ischemia / reperfusion injury407Transcriptome-based identification of new anti-inflammatory properties of the olive oil hydroxytyrosol in vascular endothelial cell under basal and proinflammatory conditions408Gene polymorphisms combinations and risk of myocardial infarctionComputer modelling, bioinformatics and big data411Comparison of the repolarization reserve in three state-of-the-art models of the human ventricular action potentialMetabolism, diabetes mellitus and obesity414Endothelial monocyte-activating polypeptide-II improves heart function in type -I Diabetes mellitus415Admission glucose level is independent predictor of impaired left ventricular function in patients with acute myocardial infarction: a two dimensional speckle-tracking echocardiography study416Association between biochemical markers of lipid profile and inflammatory reaction and stiffness of the vascular wall in hypertensive patients with abdominal obesity417Multiple common co-morbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress and myocardial stiffening418Investigating the cardiovascular effects of antiretroviral drugs in a lean and high fat/sucrose diet rat model of obesity419Statins in the treatment of non-alcoholic steatohepatitis (NASH). Our experience from a 2-year prospective study in Constanta County, Romania420Epicardial adipose tissue as a predictor of cardiovascular outcome in patients with ACS undergoing PCI?Arterial and pulmonary hypertension423Dependence between heart rhythm disorers and ID polymorphism of ACE gene in hypertensive patients424Molecular mechanisms underlying the beneficial effects of Urocortin 2 in pulmonary arterial hypertension425Inhibition of TGf-b axis and action of renin-angiotensin system in human ascending aorta aneurysms426Early signs of microcirculation and macrocirculation abnormalities in prehypertension427Vascular smooth muscle cell-expressed Tie-2 controls vascular tone428Cardiac and vascular remodelling in the development of chronic thrombo-embolic pulmonary hypertension in a novel swine modelBiomarkers431Arrhythmogenic cardiomyopathy: a new, non invasive biomarker432Can circulating microRNAs distinguish type 1 and type 2 myocardial infarction?433Design of a high-throughput multiplex proteomics assay to identify left ventricular diastolic dysfunction in diabetes434Monocyte-derived and P-selectin-carrying microparticles are differently modified by a low fat diet in patients with cardiovascular risk factors who will and who will not develop a cardiovascular event435Red blood cell distribution width assessment by polychromatic interference microscopy of thin films in chronic heart failure436Invasive and noninvasive evaluation of quality of radiofrequency-induced cardiac denervation in patients with atrial fibrillation437The effect of therapeutic hypothermia on the level of brain derived neurotrophic factor (BDNF) in sera following cardiopulmonary resustitation438Novel biomarkers to predict outcome in patients with heart failure and severe aortic stenosis439Biological factors linking depression and anxiety to cardiovascular disease440Troponins and myoglobin dynamic at coronary arteries graftingInvasive, non-invasive and molecular imaging443Diet composition effects on the genetic typing of the mouse ob mutation: a micro-ultrasound characterization of cardiac function, macro and micro circulation and liver steatosis444Characterization of pig coronary and rabbit aortic lesions using IV-OCT quantitative analysis: correlations with histologyGene therapy and cell therapy447Enhancing the survival and angiogenic potential of mouse atrial mesenchymal cells448VCAM-1 expression in experimental myocardial infarction and its relation to bone marrow-derived mononuclear cell retentionTissue engineering451Advanced multi layered scaffold that increases the maturity of stem cell-derived human cardiomyocytes452Response of engineered heart tissue to simulated ischemia/reperfusion in the presence of acute hyperglycemic conditions453Serum albumin hydrogels prevent de-differentiation of neonatal cardiomyocytes454A novel paintbrush technique for transfer of low viscosity ultraviolet light curable cyan methacrylate on saline immersed in-vitro sheep heart

Author

Garcia-Martinez, V, primary, Lopez Sanchez, C, primary, Hamed, W, primary, Hsu, JH, primary, Ferrer-Lorente, R, primary, Alshamrani, Maryam, primary, Pizzicannella, J, primary, Vindis, C, primary, Badi, I, primary, Korte, L, primary, Voellenkle, C, primary, Niculescu, L S, primary, Massaro, M, primary, Babaeva, AR, primary, Da Silva, F, primary, Woudstra, L, primary, Berezin, A, primary, Bae, MK, primary, Del Giudice, C, primary, Bageghni, S A, primary, Krobert, K, primary, Levay, M, primary, Vignier, N, primary, Ranieri, A, primary, Magenta, A, primary, Orlandi, A, primary, Porro, B, primary, Jeon, E-S, primary, Omori, Y, primary, Herold, J, primary, Barnett, G A, primary, Grochot-Przeczek, A, primary, Korpisalo, P, primary, Deffge, C, primary, Margariti, A, primary, Rong, W, primary, Maring, JA, primary, Gambardella, J, primary, Mitrofan, CG, primary, Karpinska, O, primary, Morbidelli, L, primary, Wilkinson, FL, primary, Kostina, AS, primary, De Mey, J G R, primary, Kumar, A, primary, Lupieri, A, primary, Pellet-Many, C, primary, Stamatiou, R, primary, Gromotowicz, A, primary, Dickhout, A, primary, Murina, M, primary, Roka-Moiia, YM, primary, Malinova, L, primary, Diaz-Canestro, C, primary, Vigliarolo, T, primary, Cuzzocrea, S, primary, Szantai, A, primary, Medic, B, primary, Cassambai, S, primary, Korda, A, primary, Revnic, C R, primary, Borile, G, primary, Diokmetzidou, A, primary, Murfitt, L, primary, Budko, A, primary, Fiordelisi, A, primary, De Wijs-Meijler, DPM, primary, Gevaert, AB, primary, Noriega De La Colina, A, primary, Benes, J, primary, Guillermo Solache Berrocal, GSB, primary, Gafarov, V, primary, Zhebel, VM, primary, Prakaschandra, R, primary, Stepien, E L, primary, Smith, LE, primary, Carluccio, MA, primary, Timasheva, Y, primary, Paci, M, primary, Dorofeyeva, N A, primary, Chimed, CH, primary, Petelina, TI, primary, Sorop, O, primary, Genis, A, primary, Parepa, I R, primary, Tscharre, M, primary, Krestjyaninov, MV, primary, Maia-Rocha, C, primary, Borges, L, primary, Sasonko, M L, primary, Kapel, SS, primary, Stam, K, primary, Sommariva, E, primary, Stojkovic, S, primary, O'reilly, J, primary, Chiva-Blanch, G, primary, Evtushenko, A, primary, Skopal, J, primary, Sunderland, N, primary, Gegenava, T, primary, Charnaia, MA, primary, Di Lascio, N, primary, Tarvainen, SJ, primary, Malandraki-Miller, S, primary, Uitterdijk, A, primary, Benzoni, P, primary, Ruivo, E, primary, Humphrey, E J, primary, Arokiaraj, MC, primary, Franco, D, additional, Garcia-Lopez, V, additional, Aranega, A, additional, Lopez-Sanchez, C, additional, Garcia-Martinez, V, additional, Tayel, S, additional, Khader, H, additional, El-Helbawy, N, additional, Alrefai, A, additional, El-Barbary, H, additional, Wu, JR, additional, Dai, ZK, additional, Yeh, JL, additional, Sanjurjo-Rodriguez, C, additional, Richaud-Patin, Y, additional, Blanco, FJ, additional, Badimon, L, additional, Raya, A, additional, Cahill, Paul A, additional, Diomede, F, additional, Merciaro, I, additional, Trubiani, O, additional, Nahapetyan, H, additional, Swiader, A, additional, Faccini, J, additional, Boya, P, additional, Elbaz, M, additional, Zeni, F, additional, Burba, I, additional, Bertolotti, M, additional, Capogrossi, MC, additional, Pompilio, G, additional, Raucci, A, additional, Widmer-Teske, R, additional, Dutzmann, J, additional, Bauersachs, J, additional, Donde, K, additional, Daniel, JM, additional, Sedding, DG, additional, Simionescu, N, additional, Sanda, GM, additional, Carnuta, MG, additional, Stancu, CS, additional, Popescu, AC, additional, Popescu, MR, additional, Vlad, A, additional, Dimulescu, DR, additional, Sima, AV, additional, Scoditti, E, additional, Pellegrino, M, additional, Calabriso, N, additional, Carluccio, MA, additional, Storelli, C, additional, De Caterina, R, additional, Solodenkova, KS, additional, Kalinina, EV, additional, Usachiova, MN, additional, Lappalainen, J, additional, Lee-Rueckert, M DE C, additional, Kovanen, PT, additional, Biesbroek, PS, additional, Emmens, RWE, additional, Van Rossum, AC, additional, Juffermans, LJM, additional, Niessen, JWM, additional, Krijnen, PAJ, additional, Kremzer, A, additional, Samura, T, additional, Berezina, T, additional, Gronenko, E, additional, Kim, MK, additional, Park, HJ, additional, Bae, SK, additional, Sorriento, D, additional, Ciccarelli, M, additional, Vernieri, E, additional, Campiglia, P, additional, Trimarco, B, additional, Iaccarino, G, additional, Hemmings, K E, additional, Porter, K E, additional, Ainscough, J F, additional, Drinkhill, M J, additional, Turner, N A, additional, Hiis, HG, additional, Cosson, MV, additional, Levy, FO, additional, Wieland, T, additional, Macquart, C, additional, Chatzifrangkeskou, M, additional, Evans, A, additional, Bonne, G, additional, Muchir, A, additional, Kemp, E, additional, Avkiran, M, additional, Carlomosti, F, additional, D'agostino, M, additional, Beji, S, additional, Zaccagnini, G, additional, Maimone, B, additional, Di Stefano, V, additional, De Santa, F, additional, Cordisco, S, additional, Antonini, A, additional, Ciarapica, R, additional, Dellambra, E, additional, Martelli, F, additional, Avitabile, D, additional, Scioli, MG, additional, Bielli, A, additional, Agostinelli, S, additional, Tarquini, C, additional, Tarallo, V, additional, De Falco, S, additional, Zaninoni, A, additional, Fiorelli, S, additional, Bianchi, P, additional, Teruzzi, G, additional, Squellerio, I, additional, Turnu, L, additional, Lualdi, A, additional, Tremoli, E, additional, Cavalca, V, additional, Lee, YJ, additional, Ju, ES, additional, Choi, JO, additional, Lee, GY, additional, Lim, BK, additional, Manickam, MANOJ, additional, Jung, S-H, additional, Omiya, S, additional, Otsu, K, additional, Deffge, C, additional, Nowak, S, additional, Wagner, M, additional, Braun-Dullaeus, RC, additional, Kostin, S, additional, Francke, A, additional, Subramaniam, S, additional, Kanse, SM, additional, Al-Lamee, K, additional, Schofield, CJ, additional, Egginton, S, additional, Gershlick, AH, additional, Kloska, D, additional, Kopacz, A, additional, Augustyniak, A, additional, Dulak, J, additional, Jozkowicz, A, additional, Hytonen, J, additional, Halonen, P, additional, Taavitsainen, J, additional, Tarvainen, S, additional, Hiltunen, T, additional, Liimatainen, T, additional, Kalliokoski, K, additional, Knuuti, J, additional, Yla-Herttuala, S, additional, Weinert, S, additional, Isermann, B, additional, Lee, J, additional, Herold, J, additional, Cochrane, A, additional, Kelaini, S, additional, Bojdo, J, additional, Vila Gonzalez, M, additional, Hu, Y, additional, Grieve, D, additional, Stitt, A W, additional, Zeng, L, additional, Xu, Q, additional, Margariti, A, additional, Reglin, B, additional, Xiang, W, additional, Nitzsche, B, additional, Maibier, M, additional, Pries, AR, additional, Vrijsen, KR, additional, Chamuleau, SAJ, additional, Verhage, V, additional, Metz, CHG, additional, Lodder, K, additional, Van Eeuwijk, ECM, additional, Van Dommelen, SM, additional, Doevendans, PA, additional, Smits, AM, additional, Goumans, MJ, additional, Sluijter, JPG, additional, Bova, M, additional, Loffredo, S, additional, Appleby, S, additional, Morrell, N, additional, Baranowska-Kuczko, M, additional, Kloza, M, additional, Ambrozewicz, E, additional, Kozlowski, M, additional, Malinowska, B, additional, Kozlowska, H, additional, Monti, M, additional, Terzuoli, E, additional, Ziche, M, additional, Mahmoud, AM, additional, Jones, AM, additional, Wilkinson, JA, additional, Romero, M, additional, Duarte, J, additional, Alexander, MY, additional, Faggian, G, additional, Kostareva, AA, additional, Malashicheva, AB, additional, Leurgans, TM, additional, Nguyen, TN, additional, Irmukhamedov, A, additional, Riber, LP, additional, Mcgeogh, R, additional, Comer, S, additional, Blanco Fernandez, A, additional, Ghigo, A, additional, Blaise, R, additional, Smirnova, NF, additional, Malet, N, additional, Vincent, P, additional, Limon, I, additional, Gayral, S, additional, Hirsch, E, additional, Laffargue, M, additional, Mehta, V, additional, Zachary, I, additional, Aidonidis, I, additional, Kramkowski, K, additional, Miltyk, W, additional, Kolodziejczyk, P, additional, Gradzka, A, additional, Szemraj, J, additional, Chabielska, E, additional, Dijkgraaf, I, additional, Bitsch, N, additional, Van Hoof, S, additional, Verhaegen, F, additional, Koenen, R, additional, Hackeng, TM, additional, Roshchupkin, D I, additional, Buravleva, K V, additional, Sergienko, VI, additional, Zhernossekov, DD, additional, Rybachuk, VM, additional, Grinenko, TV, additional, Furman, N, additional, Dolotovskaya, P, additional, Shamyunov, M, additional, Denisova, T, additional, Reiner, M, additional, Akhmedov, A, additional, Keller, S, additional, Miranda, M, additional, Briand, S, additional, Barile, L, additional, Kullak-Ublick, G, additional, Luscher, T, additional, Camici, G, additional, Guida, L, additional, Magnone, M, additional, Ameri, P, additional, Lazzarini, E, additional, Fresia, C, additional, Bruzzone, S, additional, Zocchi, E, additional, Di Paola, R, additional, Cordaro, M, additional, Crupi, R, additional, Siracusa, R, additional, Campolo, M, additional, Bruschetta, G, additional, Fusco, R, additional, Pugliatti, P, additional, Esposito, E, additional, Paloczi, J, additional, Ruivo, E, additional, Gaspar, R, additional, Dinnyes, A, additional, Kobolak, J, additional, Ferdinandy, P, additional, Gorbe, A, additional, Todorovic, Z, additional, Krstic, D, additional, Savic Vujovic, K, additional, Jovicic, D, additional, Basta Jovanovic, G, additional, Radojevic Skodric, S, additional, Prostran, M, additional, Dean, S, additional, Mee, CJ, additional, Harvey, KL, additional, Hussain, A, additional, Pena, C, additional, Paltineanu, B, additional, Voinea, S, additional, Revnic, F, additional, Ginghina, C, additional, Zaglia, T, additional, Ceriotti, P, additional, Campo, A, additional, Carullo, P, additional, Armani, A, additional, Coppini, R, additional, Vida, V, additional, Olivotto, I, additional, Stellin, G, additional, Rizzuto, R, additional, De Stefani, D, additional, Sandri, M, additional, Catalucci, D, additional, Mongillo, M, additional, Soumaka, E, additional, Kloukina, I, additional, Tsikitis, M, additional, Makridakis, M, additional, Varela, A, additional, Davos, C, additional, Vlachou, A, additional, Capetanaki, Y, additional, Iqbal, MM, additional, Bennett, H, additional, Davenport, B, additional, Pinali, C, additional, Cooper, G, additional, Cartwright, E, additional, Kitmitto, A, additional, Strutynska, NA, additional, Mys, LA, additional, Sagach, VF, additional, Franco, A, additional, Verzijl, A, additional, Stam, K, additional, Van Duin, R, additional, Reiss, IKM, additional, Duncker, DJ, additional, Merkus, D, additional, Shakeri, H, additional, Orije, M, additional, Leloup, AJ, additional, Van Hove, CE, additional, Van Craenenbroeck, EM, additional, De Meyer, GRY, additional, Vrints, CJ, additional, Lemmens, K, additional, Desjardins-Creapeau, L, additional, Wu, R, additional, Lamarre-Cliche, M, additional, Larochelle, P, additional, Bherer, L, additional, Girouard, H, additional, Melenovsky, M, additional, Kvasilova, A, additional, Benes, J, additional, Ruskova, K, additional, Sedmera, D, additional, Ana Barral, ABV, additional, Martin Fernandez, M, additional, Pablo Roman Garcia, PRG, additional, Juan Carlos Llosa, JCLL, additional, Manuel Naves Diaz, MND, additional, Cesar Moris, CM, additional, Jorge B Cannata-Andia, JBCA, additional, Isabel Rodriguez, IR, additional, Voevoda, M, additional, Gromova, E, additional, Maximov, V, additional, Panov, D, additional, Gagulin, I, additional, Gafarova, A, additional, Palahniuk, H, additional, Pashkova, IP, additional, Zhebel, NV, additional, Starzhynska, OL, additional, Naidoo, DP, additional, Rawojc, K, additional, Enguita, F J, additional, Grudzien, G, additional, Cordwell, SJ, additional, White, MY, additional, Massaro, M, additional, Martinelli, R, additional, Gatta, V, additional, Nasibullin, TR, additional, Erdman, VV, additional, Tuktarova, IA, additional, Mustafina, OE, additional, Hyttinen, J, additional, Severi, S, additional, Vorobyov, GG, additional, Batmyagmar, KH, additional, Lkhagvasuren, Z, additional, Gapon, LI, additional, Musikhina, NA, additional, Avdeeva, KS, additional, Dyachkov, SM, additional, Heinonen, I, additional, Van Kranenburg, M, additional, De Beer, VJ, additional, Octavia, Y, additional, Van Geuns, RJ, additional, Van Den Meiracker, AH, additional, Van Der Velden, J, additional, Everson, FP, additional, Ogundipe, T, additional, Grandjean, T, additional, De Boever, P, additional, Goswami, N, additional, Strijdom, H, additional, Suceveanu, A I, additional, Suceveanu, A P, additional, Mazilu, L, additional, Tofoleanu, D E, additional, Catrinoiu, D, additional, Rohla, M, additional, Hauser, C, additional, Huber, K, additional, Wojta, H, additional, Weiss, TW, additional, Melnikova, MA, additional, Olezov, NV, additional, Gimaev, RH, additional, Khalaf, H, additional, Ruzov, VI, additional, Adao, R, additional, Mendes-Ferreira, P, additional, Santos-Ribeiro, D, additional, Rademaker, M, additional, Leite-Moreira, AF, additional, Bras-Silva, C, additional, Alvarenga, LAA, additional, Falcao, RSP, additional, Dias, RR, additional, Lacchini, S, additional, Gutierrez, PS, additional, Michel, JB, additional, Gurfinkel, YU I, additional, Atkov, O YU, additional, Teichert, M, additional, Korn, C, additional, Mogler, C, additional, Hertel, S, additional, Arnold, C, additional, Korff, T, additional, Augustin, HG, additional, Van Duin, RWB, additional, De Wijs-Meijler, DPM, additional, D'alessandra, Y, additional, Farina, F M, additional, Casella, M, additional, Catto, V, additional, Carbucicchio, C, additional, Dello Russso, A, additional, Stadiotti, I, additional, Brambilla, S, additional, Chiesa, M, additional, Giacca, M, additional, Colombo, G I, additional, Tondo, C, additional, Ahlin, F, additional, Andric, T, additional, Tihanyi, D, additional, Wojta, J, additional, O'connell, E, additional, Butt, A, additional, Murphy, L, additional, Pennington, S, additional, Ledwidge, M, additional, Mcdonald, K, additional, Baugh, J, additional, Watson, C, additional, Suades, R, additional, Crespo, J, additional, Estruch, R, additional, Dyachenko, A, additional, Ryabukho, V, additional, Evtushenko, V, additional, Saushkina, YU, additional, Lishmanov, YU, additional, Smyshlyaev, K, additional, Bykov, A, additional, Popov, S, additional, Pavlyukova, E, additional, Anfinogenova, Y, additional, Szigetfu, E, additional, Kapornai, B, additional, Forizs, E, additional, Jenei, ZS, additional, Nagy, Z, additional, Merkely, B, additional, Zima, E, additional, Cai, A, additional, Dworakowski, R, additional, Gibbs, T, additional, Piper, S, additional, Jegard, N, additional, Mcdonagh, T, additional, Gegenava, M, additional, Dementieva, II, additional, Morozov, YUA, additional, Barsanti, C, additional, Stea, F, additional, Lenzarini, F, additional, Kusmic, C, additional, Faita, F, additional, Halonen, PJ, additional, Puhakka, PH, additional, Hytonen, JP, additional, Taavitsainen, JM, additional, Supit, E A, additional, Carr, C A, additional, Groenendijk, BCW, additional, Gorsse-Bakker, C, additional, Panasewicz, A, additional, Sneep, S, additional, Tempel, D, additional, Van Der Giessen, WJ, additional, Rys, J, additional, Daraio, C, additional, Dell'era, P, additional, Pigler, J, additional, Eder, A, additional, Eschenhagen, T, additional, Mazo, M M, additional, Amdursky, N, additional, Peters, N S, additional, Stevens, M M, additional, and Terracciano, C M, additional

Published
2016
Full Text
View/download PDF

8. The pH and ionic composition of the sub-embryonic fluid of the Japanese quail (Coturnix c. japonica)

Author

Pellet-Many, C and Baggott, Glenn K.

Subjects
sense organs, skin and connective tissue diseases, bcs
Abstract

The current theory of acid-base chemistry regards [H+] as a dependent variable: changes in pH of a fluid can only occur by alteration of strong ion concentrations ([Na+], [K+], [Cl-]). The objective of this study was to determine whether manipulation of sub-embryonic fluid strong ion composition would alter [H+] in the direction predicted by theory. Changes to fluid strong ion concentrations decreased pH in the way predicted and the changes in Cl- suggest a passive distribution. Also, changes in organic anions suggest an essential role for these in acid-base chemistry of this fluid. It was notable that both Na and HCO3- were unaffected by the treatments emphasising the importance of these two ions in fluid production by the quail blastoderm.

Published
2005

9. Neuropilins play a role in the development of neointimal hyperplasia following arterial injury by modulating vascular smooth muscle cell migration and proliferation.

Author

Pellet-Many, C., Mehta, V., Evans, I., Fields, L., Ruivo, J., and Zachary, I.

Subjects
*NEUROPILINS, *HYPERPLASIA
Abstract

An abstract of the article "Neuropilins play a role in the development of neointimal hyperplasia following arterial injury by modulating vascular smooth muscle cell migration and proliferation" by C. Pellet-Many, V. Mehta, I. Evans, L. Fields, J. Ruivo and I. Zachary is presented.

Published
2014

10. Neuropilins and vascular remodeling.

Author

Pellet-Many, C., Mehta, V., Evans, I., Ruivo, J., and Zachary, I.

Subjects
*NEUROPILINS, *POLYPEPTIDES, *IMMUNE response
Abstract

Aim: Neuropilin 1 (NRP1) and the structurally-related molecule, neuropilin 2 (NRP2), are co-receptors both for class 3 semaphorins, a family of secreted polypeptides with key roles in axonal guidance, and for various members of the VEGF family. Neuropilins were also identified to be key players in other physiological and pathological settings such as the primary immune response and cancer. Our group identified Neuropilins (NRPs) as regulators of vascular smooth muscle cell (VSMC) migration 1. In this study, we explored the role of NRP1 in abnormal VSMC accumulation in vivo in the rat carotid artery model of neointimal hyperplasia following balloon injury, in which VSMC migration and proliferation play important roles. Methods: Male Sprague-Dawley rats were subjected to balloon angioplasty and left to recover for 7,14 or 28 days. Quantitative PCR and Western blotting were used to look at endogenous levels of NRPs expression in carotid arteries at the different recovery times. At the time of surgery, we applied 30% pluronic gel containing 10E10 adenoviral (Ad) particles expressing control LacZ, NRP1 Wild-Type (WT) or a truncated form, devoid of intracytoplasmic domain (NRP1ΔC),to the adventitia. Morphometric analysis was used to quantify the intima/media ratios in adenovirus-transduced arteries; Western blot and absolute RT-qPCR were used to detect changes in protein expression and mRNA levels respectively. Results: Endogenous NRP1 and NRP2 mRNA and protein levels are upregulated after carotid injury with a maximum protein expression 7 days after injury, expression remaining elevated thereafter. Morphometric analysis of the vessels revealed that the over-expression of NRP1-WT did not alter the extent of neotinima formation but the NRP1ΔC mutant decreased the formation of neointimal hyperplasia. Conclusions: These results strongly suggest a role for NRPs in the development of neointima in the rat carotid artery model of restenosis. Insights into NRP function in the aberrant migration and proliferation of VSMC in this model could be crucial to understand the mechanism of VSMC accumulation occurring in vascular remodeling. [ABSTRACT FROM AUTHOR]

Published
2013

11. Role of neuropilins in zebrafish heart regeneration

Author

Lowe, V. J., Zachary, I., and Pellet-Many, C.

Subjects
610
Abstract

BACKGROUND: Unlike adult mammals, zebrafish can regenerate their heart. Several mechanisms are essential to achieve regeneration; these include: • the de-differentiation and proliferation of cardiomyocytes contributing to new myocardium, • angiogenesis to provide a blood supply to the injured area • epicardial activation, leading to the establishment of a scaffold for the proliferating cardiomyocytes, vessel supporting mural cells and cytokine secretion. Platelet-derived growth factor (Pdgf), Vascular endothelial growth factor (Vegf), Transforming Growth Factor beta (Tgfβ) and Fibroblast growth factor (Fgf) signalling play critical roles in the zebrafish heart regeneration. Neuropilins (NRPs) are cell surface co-receptors that have been implicated in VEGF, PDGF, FGF, TGFβ signalling. AIMS: I hypothesised that neuropilins are required for the regenerative response, and investigated the role of neuropilins in zebrafish heart regeneration following cryoinjury. RESULTS: Zebrafish have four neuropilins isoforms, nrp 1a, 1b, 2a and 2b. I found that all isoforms were upregulated in the ventricle following cardiac cryoinjury. Neuropilins were strongly expressed, at both the mRNA and protein level, by the activated epicardium and endocardium and at the injured/healthy myocardium border. Neuropilin upregulation coincides with leucocyte infiltration to the injured area, epicardial activation and initiation of neovascularisation, implicating a role of nrps in these processes. A nrp1a mutant, encoding a truncated, non-functional protein, showed a significant delay in heart regeneration in comparison to wild type fish. Furthermore, epicardial cells from nrp1a mutant zebrafish heart explants displayed an impaired response to activation by cryoinjury. CONCLUSIONS: Nrp1 plays a key role in zebrafish heart regeneration, mediated through epicardial activation and migration and likely contributes to further physiological processes in other cardiac cell-types. This is the first report of an injury-induced epicardial activation phenotype caused by the disruption of a single allele in zebrafish.

Published
2017

12. Hierarchically Structured Biodegradable Microspheres Promote Therapeutic Angiogenesis.

Author

Hendow EK, Iacoviello F, Casajuana Ester M, Pellet-Many C, and Day RM

Abstract

Promoting neovascularization is a prerequisite for many tissue engineering applications and the treatment of cardiovascular disease. Delivery of a pro-angiogenic stimulus via acellular materials offers several benefits over biological therapies but has been hampered by interaction of the implanted material with the innate immune response. However, macrophages, a key component of the innate immune response, release a plurality of soluble factors that can be harnessed to stimulate neovascularization and restore blood flow to damaged tissue. This study investigates the ability of biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres to restore tissue perfusion in a hind limb model of ischaemia. Microspheres exhibiting a hierarchical porous structure are associated with an increase in blood flow at day 21 post-implantation compared with solid microspheres composed of the same polymer. This corresponds with an increase in blood vessel density in the surrounding tissue. In vitro simulation of the foreign body response observed demonstrates M2-like macrophages incubated with the porous microspheres secreted increased amounts of vascular endothelial growth factor (VEGF) compared with M1-like macrophages providing a potential mechanism for the increased neovascularization. The results from this study demonstrate implantable biodegradable porous microspheres provide a novel approach for increasing neovascularization that could be exploited for therapeutic applications., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Published
2024
Full Text
View/download PDF

13. VEGF-A 165 -Induced Endothelial Cells Chemotactic Migration and Invasion Assays.

Author

Pellet-Many C

Subjects
Cell Movement, Chemotactic Factors, Chemotaxis physiology, Endothelial Cells, Vascular Endothelial Growth Factor A pharmacology
Abstract

In vitro assays of endothelial cell migration have led to critical insights into the mechanisms of angiogenesis. The transwell assay, or modified Boyden chamber assay was developed to investigate chemotaxis, which corresponds to the directional migration of cells in response to a chemoattractant gradient. It is a reliable and convenient assay that does not require expensive equipment.In the modified Boyden chamber assay, two compartments are separated with a porous membrane through which cells can migrate. The lower compartment contains the chemoattractant, creating a gradient by diffusing into the upper chamber containing the cells. Adherent cells will migrate through the membrane and remain on the lower side of the membrane, where they can finally be fixed, stained, and counted., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2022
Full Text
View/download PDF

14. The Zebrafish Cardiac Endothelial Cell-Roles in Development and Regeneration.

Author

Lowe V, Wisniewski L, and Pellet-Many C

Abstract

In zebrafish, the spatiotemporal development of the vascular system is well described due to its stereotypical nature. However, the cellular and molecular mechanisms orchestrating post-embryonic vascular development, the maintenance of vascular homeostasis, or how coronary vessels integrate into the growing heart are less well studied. In the context of cardiac regeneration, the central cellular mechanism by which the heart regenerates a fully functional myocardium relies on the proliferation of pre-existing cardiomyocytes; the epicardium and the endocardium are also known to play key roles in the regenerative process. Remarkably, revascularisation of the injured tissue occurs within a few hours after cardiac damage, thus generating a vascular network acting as a scaffold for the regenerating myocardium. The activation of the endocardium leads to the secretion of cytokines, further supporting the proliferation of the cardiomyocytes. Although epicardium, endocardium, and myocardium interact with each other to orchestrate heart development and regeneration, in this review, we focus on recent advances in the understanding of the development of the endocardium and the coronary vasculature in zebrafish as well as their pivotal roles in the heart regeneration process.

Published
2021
Full Text
View/download PDF

15. Microporous Biodegradable Films Promote Therapeutic Angiogenesis.

Author

Hendow EK, Moazen M, Iacoviello F, Bozec L, Pellet-Many C, and Day RM

Subjects
Animals, Biocompatible Materials, Disease Models, Animal, Hindlimb, Neovascularization, Pathologic, Ischemia therapy, Neovascularization, Physiologic
Abstract

Peripheral arterial disease and critical limb ischemia are common symptoms of cardiovascular disease. Vascular surgery is used to create a bypass around occluded blood vessels to improve blood flow to ischemic muscle, thus avoiding the need for amputation. Attempts to vascularize tissues by therapeutic angiogenesis using delivery of exogenous angiogenic agents are underwhelming. A material-based approach that provides an endogenous stimulus capable of promoting angiogenesis and increased tissue perfusion would provide a paradigm shift in treatment options available. It is reported here that microporous biodegradable films produced using thermally induced phase separation provide a localized biophysical stimulus of proangiogenic genes in vivo that is associated with increased blood vessel density and restoration of blood flow to ischemic tissue. These findings show, for the first time, that acellular, nonfunctionalized biodegradable biomaterials can provide an innovative, material-based approach for therapeutic angiogenesis to enhance tissue reperfusion in vivo., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2020
Full Text
View/download PDF

16. Emerging Roles for Neuropilin-2 in Cardiovascular Disease.

Author

Harman JL, Sayers J, Chapman C, and Pellet-Many C

Subjects
Animals, Endothelial Cells pathology, Humans, Inflammation metabolism, Inflammation pathology, Macrophages metabolism, Monocytes metabolism, Muscle, Smooth, Vascular cytology, Myocytes, Smooth Muscle cytology, Neovascularization, Pathologic, Neuropilin-2 therapeutic use, Plaque, Atherosclerotic pathology, Receptors, Cell Surface metabolism, Signal Transduction genetics, Atherosclerosis metabolism, Cardiovascular Diseases metabolism, Endothelial Cells metabolism, Myocytes, Smooth Muscle metabolism, Neuropilin-2 metabolism, Plaque, Atherosclerotic metabolism
Abstract

Cardiovascular disease, the leading cause of death worldwide, is predominantly associated with atherosclerosis. Atherosclerosis is a chronic inflammatory disease characterised by the narrowing of large to medium-sized arteries due to a build-up of plaque. Atherosclerotic plaque is comprised of lipids, extracellular matrix, and several cell types, including endothelial, immune, and vascular smooth muscle cells. Such narrowing of the blood vessels can itself restrict blood flow to vital organs but most severe clinical complications, including heart attacks and strokes, occur when lesions rupture, triggering the blood to clot and obstructing blood flow further down the vascular tree. To circumvent such obstructions, percutaneous coronary intervention or bypass grafts are often required; however, re-occlusion of the treated artery frequently occurs. Neuropilins (NRPs), a multifunctional family of cell surface co-receptors, are expressed by endothelial, immune, and vascular smooth muscle cells and are regulators of numerous signalling pathways within the vasculature. Here, we review recent studies implicating NRP2 in the development of occlusive vascular diseases and discuss how NRP2 could be targeted for therapeutic intervention.

Published
2020
Full Text
View/download PDF

17. Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart.

Author

Lowe V, Wisniewski L, Sayers J, Evans I, Frankel P, Mercader-Huber N, Zachary IC, and Pellet-Many C

Subjects
Animals, Animals, Genetically Modified, Cell Movement genetics, Cells, Cultured, Cold Temperature, Coronary Vessels physiology, Heart Injuries etiology, Heart Injuries pathology, Heart Injuries physiopathology, Myocytes, Cardiac physiology, Neuropilin-1 genetics, Rats, Zebrafish physiology, Heart physiology, Neovascularization, Physiologic genetics, Neuropilin-1 physiology, Pericardium physiology, Regeneration genetics
Abstract

Unlike adult mammals, zebrafish can regenerate their heart. A key mechanism for regeneration is the activation of the epicardium, leading to the establishment of a supporting scaffold for new cardiomyocytes, angiogenesis and cytokine secretion. Neuropilins are co-receptors that mediate signaling of kinase receptors for cytokines with crucial roles in zebrafish heart regeneration. We investigated the role of neuropilins in response to cardiac injury and heart regeneration. All four neuropilin isoforms ( nrp1a , nrp1b , nrp2a and nrp2b ) were upregulated by the activated epicardium and an nrp1a -knockout mutant showed a significant delay in heart regeneration and displayed persistent collagen deposition. The regenerating hearts of nrp1a mutants were less vascularized, and epicardial-derived cell migration and re-expression of the developmental gene wt1b was impaired. Moreover, cryoinjury-induced activation and migration of epicardial cells in heart explants were reduced in nrp1a mutants. These results identify a key role for Nrp1 in zebrafish heart regeneration, mediated through epicardial activation, migration and revascularization., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Published
2019
Full Text
View/download PDF

18. Smooth muscle cell-specific knockout of neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation.

Author

Mahmoud M, Evans IM, Mehta V, Pellet-Many C, Paliashvili K, and Zachary I

Subjects
Animals, Cell Movement physiology, Cell Proliferation physiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myofibroblasts metabolism, Neointima metabolism, Signal Transduction physiology, Vascular Endothelial Growth Factor A metabolism, Lung metabolism, Muscle, Smooth, Vascular metabolism, Myocytes, Smooth Muscle metabolism, Neuropilin-1 metabolism
Abstract

Neuropilin 1 (NRP1) is important for neuronal and cardiovascular development due to its role in conveying class 3 semaphorin and vascular endothelial growth factor signaling, respectively. NRP1 is expressed in smooth muscle cells (SMCs) and mediates their migration and proliferation in cell culture and is implicated in pathological SMC remodeling in vivo. To address the importance of Nrp1 for SMC function during development, we generated conditional inducible Nrp1 SMC-specific knockout mice. Induction of early postnatal SMC-specific Nrp1 knockout led to pulmonary hemorrhage associated with defects in alveogenesis and revealed a specific requirement for Nrp1 in myofibroblast recruitment to the alveolar septae and PDGF-AA-induced migration in vitro. Furthermore, SMC-specific Nrp1 knockout inhibited PDGF-BB-stimulated SMC outgrowth ex vivo in aortic ring assays and reduced pathological arterial neointima formation in vivo. In contrast, we observed little significant effect of SMC-specific Nrp1 knockout on neonatal retinal vascularization. Our results point to a requirement of Nrp1 in vascular smooth muscle and myofibroblast function in vivo, which may have relevance for postnatal lung development and for pathologies characterized by excessive SMC and/or myofibroblast proliferation.

Published
2019
Full Text
View/download PDF

19. VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy-Terminal NRP1 Fragments That Regulate Angiogenic Signaling.

Author

Mehta V, Fields L, Evans IM, Yamaji M, Pellet-Many C, Jones T, Mahmoud M, and Zachary I

Subjects
ADAMTS Proteins genetics, ADAMTS9 Protein genetics, Animals, Cell Movement drug effects, Cells, Cultured, Coculture Techniques, Human Umbilical Vein Endothelial Cells enzymology, Humans, Mice, Neuropilin-1 genetics, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, Proteolysis, Signal Transduction drug effects, Vascular Endothelial Growth Factor Receptor-2 metabolism, ADAMTS Proteins metabolism, ADAMTS9 Protein metabolism, Angiogenesis Inducing Agents pharmacology, Human Umbilical Vein Endothelial Cells drug effects, Neovascularization, Physiologic drug effects, Neuropilin-1 metabolism, Peptide Fragments metabolism, Vascular Endothelial Growth Factor A pharmacology
Abstract

Objective- NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. Here, we characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function. Approach and Results- NRP1 species comprising the carboxy (C)-terminal and transmembrane NRP1 domains but lacking the ligand-binding A and B regions are constitutively expressed in endothelial cells. Generation of these C-terminal domain NRP1 proteins is upregulated by phorbol ester and Ca 2+ ionophore, and reduced by pharmacological inhibition of metalloproteinases, by small interfering RNA-mediated knockdown of 2 members of ADAM (a disintegrin and metalloproteinase) family, ADAMs 9 and 10, and by a specific ADAM10 inhibitor. Furthermore, VEGF upregulates expression of these NRP1 species in an ADAM9/10-dependent manner. Transduction of endothelial cells with adenoviral constructs expressing NRP1 C-terminal domain fragments inhibited VEGF-induced phosphorylation of VEGFR2 (VEGF receptor tyrosine kinase)/KDR (kinase domain insert receptor) and decreased VEGF-stimulated endothelial cell motility and angiogenesis in coculture and aortic ring sprouting assays. Conclusions- These findings identify novel NRP1 species in endothelial cells and demonstrate that regulation of NRP1 proteolysis via ADAMs 9 and 10 is a new regulatory pathway able to modulate VEGF angiogenic signaling.

Published
2018
Full Text
View/download PDF

20. Receptor Tyrosine Kinase Ubiquitination and De-Ubiquitination in Signal Transduction and Receptor Trafficking.

Author

Critchley WR, Pellet-Many C, Ringham-Terry B, Harrison MA, Zachary IC, and Ponnambalam S

Abstract

Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes. The ubiquitin ligase superfamily comprising the E1, E2 and E3 enzymes are increasingly implicated in this post-translational modification by adding mono- and polyubiquitin tags to RTKs. Conversely, removal of these ubiquitin tags by proteases called de-ubiquitinases (DUBs) enables RTK recycling for another round of ligand sensing and signal transduction. The endocytosis of basal and activated RTKs from the plasma membrane is closely linked to controlled proteolysis after trafficking and delivery to late endosomes and lysosomes. Proteolytic RTK fragments can also have the capacity to move to compartments such as the nucleus and regulate gene expression. Such mechanistic diversity now provides new opportunities for modulating RTK-regulated cellular responses in health and disease states., Competing Interests: The authors declare no conflict of interest.

Published
2018
Full Text
View/download PDF

21. Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury.

Author

Pellet-Many C, Mehta V, Fields L, Mahmoud M, Lowe V, Evans I, Ruivo J, and Zachary I

Subjects
Angioplasty, Balloon adverse effects, Animals, Carotid Artery Injuries etiology, Carotid Artery Injuries pathology, Cell Movement, Cell Proliferation, Disease Models, Animal, Endothelium, Vascular pathology, Endothelium, Vascular physiology, Hyperplasia, Male, Myocytes, Smooth Muscle metabolism, Neointima etiology, Neointima pathology, Platelet-Derived Growth Factor metabolism, Rats, Sprague-Dawley, Up-Regulation, Carotid Artery Injuries metabolism, Neointima metabolism, Neuropilin-1 metabolism, Neuropilin-2 metabolism
Abstract

Aims: Neuropilins 1 and 2 (NRP1 and NRP2) play crucial roles in endothelial cell migration contributing to angiogenesis and vascular development. Both NRPs are also expressed by cultured vascular smooth muscle cells (VSMCs) and are implicated in VSMC migration stimulated by PDGF-BB, but it is unknown whether NRPs are relevant for VSMC function in vivo. We investigated the role of NRPs in the rat carotid balloon injury model, in which endothelial denudation and arterial stretch induce neointimal hyperplasia involving VSMC migration and proliferation., Methods and Results: NRP1 and NRP2 mRNAs and proteins increased significantly following arterial injury, and immunofluorescent staining revealed neointimal NRP expression. Down-regulation of NRP1 and NRP2 using shRNA significantly reduced neointimal hyperplasia following injury. Furthermore, inhibition of NRP1 by adenovirally overexpressing a loss-of-function NRP1 mutant lacking the cytoplasmic domain (ΔC) reduced neointimal hyperplasia, whereas wild-type (WT) NRP1 had no effect. NRP-targeted shRNAs impaired, while overexpression of NRP1 WT and NRP1 ΔC enhanced, arterial re-endothelialization 14 days after injury. Knockdown of either NRP1 or NRP2 inhibited PDGF-BB-induced rat VSMC migration, whereas knockdown of NRP2, but not NRP1, reduced proliferation of cultured rat VSMC and neointimal VSMC in vivo. NRP knockdown also reduced the phosphorylation of PDGFα and PDGFβ receptors in rat VSMC, which mediate VSMC migration and proliferation., Conclusion: NRP1 and NRP2 play important roles in the regulation of neointimal hyperplasia in vivo by modulating VSMC migration (via NRP1 and NRP2) and proliferation (via NRP2), independently of the role of NRPs in re-endothelialization., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2015
Full Text
View/download PDF

22. Chemotactic Migration of Endothelial Cells Towards VEGF-A₁₆₅.

Author

Pellet-Many C

Subjects
Humans, In Vitro Techniques, Chemotaxis, Endothelial Cells physiology, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A metabolism
Abstract

In vitro assays of endothelial cell migration have led to critical insights into the mechanisms of angiogenesis. The transwell assay, or modified Boyden chamber assay was developed to investigate chemotaxis, which corresponds to the directional migration of cells in response to a chemoattractant gradient. It is a robust and easy-to-use assay that does not require expensive equipment. In the modified Boyden chamber assay, two compartments are separated with a porous membrane through which cells can migrate. The lower compartment contains the chemoattractant, creating a gradient by diffusing into the upper chamber containing the cells. The cells will migrate through the membrane and remain on the lower side of the membrane, where they can finally be fixed and counted.

Published
2015
Full Text
View/download PDF

23. A crucial role for DOK1 in PDGF-BB-stimulated glioma cell invasion through p130Cas and Rap1 signalling.

Author

Barrett A, Evans IM, Frolov A, Britton G, Pellet-Many C, Yamaji M, Mehta V, Bandopadhyay R, Li N, Brandner S, Zachary IC, and Frankel P

Subjects
Becaplermin, Brain Neoplasms pathology, Cell Line, Tumor, Chemotaxis, Glioblastoma pathology, Humans, Neoplasm Invasiveness, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation, Protein Processing, Post-Translational, Shelterin Complex, Signal Transduction, src-Family Kinases metabolism, Brain Neoplasms metabolism, Crk-Associated Substrate Protein metabolism, DNA-Binding Proteins physiology, Glioblastoma metabolism, Phosphoproteins physiology, Proto-Oncogene Proteins c-sis physiology, RNA-Binding Proteins physiology, Telomere-Binding Proteins metabolism
Abstract

DOK1 regulates platelet-derived growth factor (PDGF)-BB-stimulated glioma cell motility. Mechanisms regulating tumour cell motility are essential for invasion and metastasis. We report here that PDGF-BB-mediated glioma cell invasion and migration are dependent on the adaptor protein downstream of kinase 1 (DOK1). DOK1 is expressed in several glioma cell lines and in tumour biopsies from high-grade gliomas. DOK1 becomes tyrosine phosphorylated upon PDGF-BB stimulation of human glioma cells. Knockdown of DOK1 or expression of a DOK1 mutant (DOK1FF) containing Phe in place of Tyr at residues 362 and 398, resulted in inhibition of both the PDGF-BB-induced tyrosine phosphorylation of p130Cas (also known as BCAR1) and the activation of Rap1. DOK1 colocalises with tyrosine phosphorylated p130Cas at the cell membrane of PDGF-BB-treated cells. Expression of a non-tyrosine-phosphorylatable substrate domain mutant of p130Cas (p130Cas15F) inhibited PDGF-BB-mediated Rap1 activation. Knockdown of DOK1 and Rap1 inhibited PDGF-BB-induced chemotactic cell migration, and knockdown of DOK1 and Rap1 and expression of DOK1FF inhibited PDGF-mediated three-dimensional (3D) spheroid invasion. These data show a crucial role for DOK1 in the regulation of PDGF-BB-mediated tumour cell motility through a p130Cas-Rap1 signalling pathway. [Corrected], (© 2014. Published by The Company of Biologists Ltd.)

Published
2014
Full Text
View/download PDF

24. Endosome-to-Plasma Membrane Recycling of VEGFR2 Receptor Tyrosine Kinase Regulates Endothelial Function and Blood Vessel Formation.

Author

Jopling HM, Odell AF, Pellet-Many C, Latham AM, Frankel P, Sivaprasadarao A, Walker JH, Zachary IC, and Ponnambalam S

Abstract

Rab GTPases are implicated in endosome-to-plasma membrane recycling, but how such membrane traffic regulators control vascular endothelial growth factor receptor 2 (VEGFR2/KDR) dynamics and function are not well understood. Here, we evaluated two different recycling Rab GTPases, Rab4a and Rab11a, in regulating endothelial VEGFR2 trafficking and signalling with implications for endothelial cell migration, proliferation and angiogenesis. In primary endothelial cells, VEGFR2 displays co-localisation with Rab4a, but not Rab11a GTPase, on early endosomes. Expression of a guanosine diphosphate (GDP)-bound Rab4a S22N mutant caused increased VEGFR2 accumulation in endosomes. TfR and VEGFR2 exhibited differences in endosome-to-plasma membrane recycling in the presence of chloroquine. Depletion of Rab4a, but not Rab11a, levels stimulated VEGF-A-dependent intracellular signalling. However, depletion of either Rab4a or Rab11a levels inhibited VEGF-A-stimulated endothelial cell migration. Interestingly, depletion of Rab4a levels stimulated VEGF-A-regulated endothelial cell proliferation. Rab4a and Rab11a were also both required for endothelial tubulogenesis. Evaluation of a transgenic zebrafish model showed that both Rab4 and Rab11a are functionally required for blood vessel formation and animal viability. Rab-dependent endosome-to-plasma membrane recycling of VEGFR2 is important for intracellular signalling, cell migration and proliferation during angiogenesis.

Published
2014
Full Text
View/download PDF

25. p130Cas: a key signalling node in health and disease.

Author

Barrett A, Pellet-Many C, Zachary IC, Evans IM, and Frankel P

Subjects
Cardiovascular System metabolism, Crk-Associated Substrate Protein analysis, Guanine Nucleotide Exchange Factors metabolism, Humans, Mechanotransduction, Cellular, Neoplasms metabolism, Neoplasms pathology, Phosphorylation, Crk-Associated Substrate Protein metabolism, Signal Transduction
Abstract

p130Cas/breast cancer anti-oestrogen resistance 1 (BCAR1) is a member of the Cas (Crk-associated substrate) family of adaptor proteins, which have emerged as key signalling nodes capable of interactions with multiple proteins, with important regulatory roles in normal and pathological cell function. The Cas family of proteins is characterised by the presence of multiple conserved motifs for protein-protein interactions, and by extensive tyrosine and serine phosphorylations. Recent studies show that p130Cas contributes to migration, cell cycle control and apoptosis. p130Cas is essential during early embryogenesis, with a critical role in cardiovascular development. Furthermore, p130Cas has been reported to be involved in the development and progression of several human cancers. p130Cas is able to perform roles in multiple processes due to its capacity to regulate a diverse array of signalling pathways, transducing signals from growth factor receptor tyrosine kinases, non-receptor tyrosine kinases, and integrins. In this review we summarise the current understanding of the structure, function, and regulation of p130Cas, and discuss the importance of p130Cas in both physiological and pathophysiological settings, with a focus on the cardiovascular system and cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Published
2013
Full Text
View/download PDF

26. A heat-shock protein axis regulates VEGFR2 proteolysis, blood vessel development and repair.

Author

Bruns AF, Yuldasheva N, Latham AM, Bao L, Pellet-Many C, Frankel P, Stephen SL, Howell GJ, Wheatcroft SB, Kearney MT, Zachary IC, and Ponnambalam S

Subjects
Animals, Arteries drug effects, Arteries physiology, Benzoquinones pharmacology, Blood Vessels drug effects, Blood Vessels metabolism, Cell Movement drug effects, Clathrin metabolism, Endocytosis drug effects, HSP70 Heat-Shock Proteins metabolism, HSP90 Heat-Shock Proteins antagonists & inhibitors, HSP90 Heat-Shock Proteins metabolism, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Humans, Intracellular Space drug effects, Intracellular Space metabolism, Lactams, Macrocyclic pharmacology, Mice, Mice, Inbred C57BL, Models, Biological, Protein Stability drug effects, Protein Transport drug effects, Regeneration drug effects, Zebrafish, Blood Vessels growth & development, Heat-Shock Proteins metabolism, Neovascularization, Physiologic drug effects, Proteolysis drug effects, Signal Transduction drug effects, Vascular Endothelial Growth Factor Receptor-2 metabolism, Wound Healing drug effects
Abstract

Vascular endothelial growth factor A (VEGF-A) binds to the VEGFR2 receptor tyrosine kinase, regulating endothelial function, vascular physiology and angiogenesis. However, the mechanism underlying VEGFR2 turnover and degradation in this response is unclear. Here, we tested a role for heat-shock proteins in regulating the presentation of VEGFR2 to a degradative pathway. Pharmacological inhibition of HSP90 stimulated VEGFR2 degradation in primary endothelial cells and blocked VEGF-A-stimulated intracellular signaling via VEGFR2. HSP90 inhibition stimulated the formation of a VEGFR2-HSP70 complex. Clathrin-mediated VEGFR2 endocytosis is required for this HSP-linked degradative pathway for targeting VEGFR2 to the endosome-lysosome system. HSP90 perturbation selectively inhibited VEGF-A-stimulated human endothelial cell migration in vitro. A mouse femoral artery model showed that HSP90 inhibition also blocked blood vessel repair in vivo consistent with decreased endothelial regeneration. Depletion of either HSP70 or HSP90 caused defects in blood vessel formation in a transgenic zebrafish model. We conclude that perturbation of the HSP70-HSP90 heat-shock protein axis stimulates degradation of endothelial VEGFR2 and modulates VEGF-A-stimulated intracellular signaling, endothelial cell migration, blood vessel development and repair.

Published
2012
Full Text
View/download PDF

27. VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation.

Author

Herzog B, Pellet-Many C, Britton G, Hartzoulakis B, and Zachary IC

Subjects
Animals, Binding Sites, Cell Adhesion, Cell Movement, Coculture Techniques, Dimerization, Endothelial Cells cytology, Endothelium, Vascular cytology, Focal Adhesion Kinase 1 genetics, Humans, Mutation, Neovascularization, Physiologic, Neuropilin-1 genetics, Phosphorylation, Plasmids, Protein Binding, Transfection, Umbilical Veins cytology, Umbilical Veins metabolism, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor Receptor-2 genetics, Endothelial Cells metabolism, Endothelium, Vascular metabolism, Focal Adhesion Kinase 1 metabolism, Focal Adhesions metabolism, Neuropilin-1 metabolism, Signal Transduction physiology, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-2 metabolism
Abstract

In endothelial cells, neuropilin-1 (NRP1) binds vascular endothelial growth factor (VEGF)-A and is thought to act as a coreceptor for kinase insert domain-containing receptor (KDR) by associating with KDR and enhancing VEGF signaling. Here we report mutations in the NRP1 b1 domain (Y297A and D320A), which result in complete loss of VEGF binding. Overexpression of Y297A and D320A NRP1 in human umbilical vein endothelial cells reduced high-affinity VEGF binding and migration toward a VEGF gradient, and markedly inhibited VEGF-induced angiogenesis in a coculture cell model. The Y297A NRP1 mutant also disrupted complexation between NRP1 and KDR and decreased VEGF-dependent phosphorylation of focal adhesion kinase at Tyr407, but had little effect on other signaling pathways. Y297A NRP1, however, heterodimerized with wild-type NRP1 and NRP2 indicating that nonbinding NRP1 mutants can act in a dominant-negative manner through formation of NRP1 dimers with reduced binding affinity for VEGF. These findings indicate that VEGF binding to NRP1 has specific effects on endothelial cell signaling and is important for endothelial cell migration and angiogenesis mediated via complex formation between NRP1 and KDR and increased signaling to focal adhesions. Identification of key residues essential for VEGF binding and biological functions provides the basis for a rational design of antagonists of VEGF binding to NRP1.

Published
2011
Full Text
View/download PDF

28. Neuropilin-1 mediates PDGF stimulation of vascular smooth muscle cell migration and signalling via p130Cas.

Author

Pellet-Many C, Frankel P, Evans IM, Herzog B, Jünemann-Ramírez M, and Zachary IC

Subjects
Adenoviridae, Cell Movement, Cells, Cultured, Chemotaxis, Crk-Associated Substrate Protein genetics, Endothelial Cells, Humans, Mutation, Myocytes, Smooth Muscle cytology, Neuropilin-1 genetics, Platelet-Derived Growth Factor genetics, Crk-Associated Substrate Protein metabolism, Muscle, Smooth, Vascular cytology, Myocytes, Smooth Muscle metabolism, Neuropilin-1 metabolism, Platelet-Derived Growth Factor metabolism, Signal Transduction physiology
Abstract

NRP1 (neuropilin-1) is a co-receptor for members of the VEGF (vascular endothelial growth factor) family in endothelial cells, but is increasingly implicated in signalling induced by other growth factors. NRP1 is expressed in VSMCs (vascular smooth muscle cells), but its function and the mechanisms involved are poorly understood. The present study aimed to determine the role of NRP1 in the migratory response of HCASMCs (human coronary artery smooth muscle cells) to PDGF (platelet-derived growth factor), and to identify the signalling mechanisms involved. NRP1 is highly expressed in HAoSMCs (human aortic smooth muscle cells) and HCASMCs, and modified in VSMCs by CS (chondroitin sulfate)-rich O-linked glycosylation at Ser612. HCASMC migration induced by PDGF-BB and PDGF-AA was inhibited by NRP1 siRNA (small interfering RNA), and by adenoviral overexpression of an NRP1 mutant lacking the intracellular domain (Ad.NRP1ΔC). NRP1 co-immunoprecipitated with PDGFRα (PDGF receptor α), and immunofluorescent staining indicated that NRP1 and PDGFRα co-localized in VSMCs. NRP1 siRNA also inhibited PDGF-induced PDGFRα activation. NRP1-specific siRNA, Ad.NRP1ΔC and removal of CS glycans using chondroitinase all inhibited PDGF-BB and -AA stimulation of tyrosine phosphorylation of the adapter protein, p130Cas (Cas is Crk-associated substrate), with little effect on other major signalling pathways, and p130Cas knockdown inhibited HCASMC migration. Chemotaxis and p130Cas phosphorylation induced by PDGF were inhibited by chondroitinase, and, additionally, adenoviral expression of a non-glycosylatable NRP1S612A mutant inhibited chemotaxis, but not p130Cas phosphorylation. These results indicate a role for NRP1 and NRP1 glycosylation in mediating PDGF-induced VSMC migration, possibly by acting as a co-receptor for PDGFRα and via selective mobilization of a novel p130Cas tyrosine phosphorylation pathway.

Published
2011
Full Text
View/download PDF

29. Neuropilin-1 signaling through p130Cas tyrosine phosphorylation is essential for growth factor-dependent migration of glioma and endothelial cells.

Author

Evans IM, Yamaji M, Britton G, Pellet-Many C, Lockie C, Zachary IC, and Frankel P

Subjects
Cell Line, Cell Line, Tumor, Crk-Associated Substrate Protein genetics, Endothelial Cells cytology, Gene Expression Regulation, Neoplastic, Gene Silencing, Glioma genetics, Hepatocyte Growth Factor metabolism, Humans, Mutation, Neuropilin-1 genetics, Phosphorylation, Platelet-Derived Growth Factor metabolism, Tyrosine metabolism, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-2 metabolism, Cell Movement, Crk-Associated Substrate Protein metabolism, Endothelial Cells metabolism, Glioma metabolism, Neuropilin-1 metabolism
Abstract

Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF) and plays an important role in mediating cell motility. However, the NRP1 signaling pathways important for cell motility are poorly understood. Here we report that p130(Cas) tyrosine phosphorylation is stimulated by hepatocyte growth factor and platelet-derived growth factor in U87MG glioma cells and VEGF in endothelial cells and is dependent on NRP1 via its intracellular domain. In endothelial cells, NRP1 silencing reduced, but did not prevent, VEGF receptor 2 (VEGFR2) phosphorylation, while expression of a mutant form of NRP1 lacking the intracellular domain (NRP1ΔC) did not affect receptor phosphorylation in U87MG cells or human umbilical vein endothelial cells (HUVECs). In HUVECs, NRP1 was also required for VEGF-induced phosphorylation of proline-rich tyrosine kinase 2, which was necessary for p130(Cas) phosphorylation. Importantly, knockdown of NRP1 or p130(Cas) or expression of either NRP1ΔC or a non-tyrosine-phosphorylatable substrate domain mutant protein (p130(Cas15F)) was sufficient to inhibit growth factor-mediated migration of glioma and endothelial cells. These data demonstrate for the first time the importance of the NRP1 intracellular domain in mediating a specific signaling pathway downstream of several receptor tyrosine kinases and identify a critical role for a novel NRP1-p130(Cas) pathway in the regulation of chemotaxis.

Published
2011
Full Text
View/download PDF

30. The role of neuropilins in cell signalling.

Author

Zachary IC, Frankel P, Evans IM, and Pellet-Many C

Subjects
Animals, Endothelial Cells metabolism, Humans, Neurons metabolism, Neuropilins genetics, Protein Isoforms genetics, Protein Isoforms metabolism, Protein Structure, Tertiary, Receptors, Vascular Endothelial Growth Factor metabolism, Vascular Endothelial Growth Factors metabolism, Neuropilins metabolism, Signal Transduction physiology
Abstract

NRPs (neuropilins) are receptors for class 3 semaphorins, polypeptides essential for axonal guidance, and for members of the VEGF (vascular endothelial growth factor) family of angiogenic cytokines. While mutant mouse studies show that NRP1 is essential for neuronal and cardiovascular development, little is known concerning the molecular mechanisms through which NRPs mediate the functions of their ligands in different cell types. NRP1 forms complexes with its co-receptors and is required for optimal function, but NRPs lack a clearly defined signalling domain and the role of NRP1 in receptor signalling and the function of the NRP1 cytosolic domain are unclear. Growing evidence indicates, however, that NRP1 plays a selective role in signalling at least in part via its C-terminal domain and interaction with intracellular binding partners.

Published
2009
Full Text
View/download PDF

31. Chondroitin sulphate-modified neuropilin 1 is expressed in human tumour cells and modulates 3D invasion in the U87MG human glioblastoma cell line through a p130Cas-mediated pathway.

Author

Frankel P, Pellet-Many C, Lehtolainen P, D'Abaco GM, Tickner ML, Cheng L, and Zachary IC

Subjects
Amino Acid Sequence, Animals, Cell Line, Tumor, Glioblastoma genetics, Humans, Mice, Molecular Sequence Data, Neoplasm Invasiveness, Neuropilin-1 biosynthesis, RNA Interference, Rats, Swine, Chondroitin Sulfates physiology, Crk-Associated Substrate Protein physiology, Glioblastoma metabolism, Glioblastoma pathology, Neuropilin-1 genetics, Signal Transduction physiology
Abstract

Neuropilin 1 (NRP1), a non-tyrosine kinase receptor for vascular endothelial growth factor and class 3 Semaphorins, is highly expressed in many human tumour cell lines, but its function is poorly understood. Here, we describe the expression of a new chondroitin sulphate-modified NRP1 (NRP1-CS) in human tumour cell lines. Expression of a non-modifiable NRP1 mutant (S612A) in U87MG human glioma cells results in enhanced invasion in three dimensions (3D), whereas wild-type NRP1 has no effect. Furthermore, the S612A NRP1 cells show a significant increase in p130Cas tyrosine phosphorylation compared with control and wild-type NRP1 cells. Silencing of p130Cas in S612A NRP1 cells resulted in a loss of increased invasive phenotype. Interestingly, p130Cas silencing does not inhibit basal 3D invasion, but leads to a mesenchymal to amoeboid transition. Biopsies from both low- and high-grade human gliomas show strong expression of NRP1, and little expression of NRP1-CS. Our data establish distinct roles for NRP1 and NRP1-CS in modulating a new NRP1-p130Cas signalling pathway contributing to glioblastoma cell invasion in 3D.

Published
2008
Full Text
View/download PDF

32. Neuropilins: structure, function and role in disease.

Author

Pellet-Many C, Frankel P, Jia H, and Zachary I

Subjects
Animals, Disease, Gene Expression Regulation, Genome genetics, Humans, Ligands, Neuropilins genetics, Protein Processing, Post-Translational, Neuropilins chemistry, Neuropilins metabolism
Abstract

NRPs (neuropilins) are co-receptors for class 3 semaphorins, polypeptides with key roles in axonal guidance, and for members of the VEGF (vascular endothelial growth factor) family of angiogenic cytokines. They lack a defined signalling role, but are thought to mediate functional responses as a result of complex formation with other receptors, such as plexins in the case of semaphorins and VEGF receptors (e.g. VEGFR2). Mutant mouse studies show that NRP1 is essential for neuronal and cardiovascular development, whereas NRP2 has a more restricted role in neuronal patterning and lymphangiogenesis, but recent findings indicate that NRPs may have additional biological roles in other physiological and disease-related settings. In particular, NRPs are highly expressed in diverse tumour cell lines and human neoplasms and have been implicated in tumour growth and vascularization in vivo. However, despite the wealth of information regarding the probable biological roles of these molecules, many aspects of the regulation of cellular function via NRPs remain uncertain, and little is known concerning the molecular mechanisms through which NRPs mediate the functions of their various ligands in different cell types.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results