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2. A loss-of-function HCN4 mutation associated with familial benign myoclonic epilepsy in infancy causes increased neuronal excitability

Author

Campostrini, G, Difrancesco, J, Castellotti, B, Milanesi, R, Gnecchi-Ruscone, T, Bonzanni, M, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Difrancesco, JC, Freri, Elena, Labate, Angelo, Campostrini, G, Difrancesco, J, Castellotti, B, Milanesi, R, Gnecchi-Ruscone, T, Bonzanni, M, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Difrancesco, JC, Freri, Elena, and Labate, Angelo

Abstract

HCN channels are highly expressed and functionally relevant in neurons and increasing evidence demonstrates their involvement in the etiology of human epilepsies. Among HCN isoforms, HCN4 is important in cardiac tissue, where it underlies pacemaker activity. Despite being expressed also in deep structures of the brain, mutations of this channel functionally shown to be associated with epilepsy have not been reported yet. Using Next Generation Sequencing for the screening of patients with idiopathic epilepsy, we identified the p.Arg550Cys (c.1648C>T) heterozygous mutation on HCN4 in two brothers affected by benign myoclonic epilepsy of infancy. Functional characterization in heterologous expression system and in neurons showed that the mutation determines a loss of function of HCN4 contribution to activity and an increase of neuronal discharge, potentially predisposing to epilepsy. Expressed in cardiomyocytes, mutant channels activate at slightly more negative voltages than wild-type (WT), in accordance with borderline bradycardia. While HCN4 variants have been frequently associated with cardiac arrhythmias, these data represent the first experimental evidence that functional alteration of HCN4 can also be involved in human epilepsy through a loss-of-function effect and associated increased neuronal excitability. Since HCN4 appears to be highly expressed in deep brain structures only early during development, our data provide a potential explanation for a link between dysfunctional HCN4 and infantile epilepsy. These findings suggest that it may be useful to include HCN4 screening to extend the knowledge of the genetic causes of infantile epilepsies, potentially paving the way for the identification of innovative therapeutic strategies.

Published
2018

3. A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability

Author

Bonzanni, M, Difrancesco, J, Milanesi, R, Campostrini, G, Castellotti, B, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Rivolta, I, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Bonzanni, Mattia, DiFrancesco, Jacopo C., Milanesi, Raffaella, Campostrini, Giulia, Castellotti, Barbara, Bucchi, Annalisa, Baruscotti, Mirko, Ferrarese, Carlo, Franceschetti, Silvana, Canafoglia, Laura, Ragona, Francesca, Freri, Elena, Labate, Angelo, Gambardella, Antonio, Costa, Cinzia, RIVOLTA, ILARIA, Gellera, Cinzia, Granata, Tiziana, Barbuti, Andrea, DiFrancesco, Dario, Bonzanni, M, Difrancesco, J, Milanesi, R, Campostrini, G, Castellotti, B, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Rivolta, I, Gellera, C, Granata, T, Barbuti, A, Difrancesco, D, Bonzanni, Mattia, DiFrancesco, Jacopo C., Milanesi, Raffaella, Campostrini, Giulia, Castellotti, Barbara, Bucchi, Annalisa, Baruscotti, Mirko, Ferrarese, Carlo, Franceschetti, Silvana, Canafoglia, Laura, Ragona, Francesca, Freri, Elena, Labate, Angelo, Gambardella, Antonio, Costa, Cinzia, RIVOLTA, ILARIA, Gellera, Cinzia, Granata, Tiziana, Barbuti, Andrea, and DiFrancesco, Dario

Abstract

The causes of genetic epilepsies are unknown in the majority of patients. HCN ion channels have a widespread expression in neurons and increasing evidence demonstrates their functional involvement in human epilepsies. Among the four known isoforms, HCN1 is the most expressed in the neocortex and hippocampus and de novo HCN1 point mutations have been recently associated with early infantile epileptic encephalopathy. So far, HCN1 mutations have not been reported in patients with idiopathic epilepsy. Using a Next Generation Sequencing approach, we identified the de novo heterozygous p.Leu157Val (c.469C > G) novel mutation in HCN1 in an adult male patient affected by genetic generalized epilepsy (GGE), with normal cognitive development. Electrophysiological analysis in heterologous expression model (CHO cells) and in neurons revealed that L157V is a loss-of-function, dominant negative mutation causing reduced HCN1 contribution to net inward current and responsible for an increased neuronal firing rate and excitability, potentially predisposing to epilepsy. These data represent the first evidence that autosomal dominant missense mutations of HCN1 can also be involved in GGE, without the characteristics of epileptic encephalopathy reported previously. It will be important to include HCN1 screening in patients with GGE, in order to extend the knowledge of the genetic causes of idiopathic epilepsies, thus paving the way for the identification of innovative therapeutic strategies.

Published
2018

4. The expression of the rare caveolin-3 variant T78M alters cardiac ion channels function and membrane excitability

Author

Campostrini, G, Bonzanni, M, Lissoni, A, Bazzini, C, Milanesi, R, Vezzoli, E, Francolini, M, Baruscotti, M, Bucchi, A, Rivolta, I, Fantini, M, Severi, S, Cappato, R, Crotti, L, Schwartz, P, Di Francesco, D, Barbuti, A, Campostrini, G, Bonzanni, M, Lissoni, A, Bazzini, C, Milanesi, R, Vezzoli, E, Francolini, M, Baruscotti, M, Bucchi, A, Rivolta, I, Fantini, M, Severi, S, Cappato, R, Crotti, L, Schwartz, P, Di Francesco, D, and Barbuti, A

Abstract

Aims Caveolinopathies are a family of genetic disorders arising from alterations of the caveolin-3 (cav-3) gene. The T78M cav-3 variant has been associated with both skeletal and cardiac muscle pathologies but its functional contribution, especially to cardiac diseases, is still controversial. Here, we evaluated the effect of the T78M cav-3 variant on cardiac ion channel function and membrane excitability. Methods and results We transfected either the wild type (WT) or T78M cav-3 in caveolin-1 knock-out mouse embryonic fibroblasts and found by immunofluorescence and electron microscopy that both are expressed at the plasma membrane and form caveolae. Two ion channels known to interact and co-immunoprecipitate with the cav-3, hKv1.5 and hHCN4, interact also with T78M cav-3 and reside in lipid rafts. Electrophysiological analysis showed that the T78M cav-3 causes hKv1.5 channels to activate and inactivate at more hyperpolarized potentials and the hHCN4 channels to activate at more depolarized potentials, in a dominant way. In spontaneously beating neonatal cardiomyocytes, the expression of the T78M cav-3 significantly increased action potential peak-to-peak variability without altering neither the mean rate nor the maximum diastolic potential. We also found that in a small cohort of patients with supraventricular arrhythmias, the T78M cav-3 variant is more frequent than in the general population. Finally, in silico analysis of both sinoatrial and atrial cell models confirmed that the T78M-dependent changes are compatible with a pro-arrhythmic effect. Conclusion This study demonstrates that the T78M cav-3 induces complex modifications in ion channel function that ultimately alter membrane excitability. The presence of the T78M cav-3 can thus generate a susceptible substrate that, in concert with other structural alterations and/or genetic mutations, may become arrhythmogenic

Published
2017

5. Epigenetics in Cardiac Health and Disease225miR-218 and mi-R34a drive persistent myocardial oxidative stress by targeting chromatin remodelers DNMT3b and SIRT1: new mechanistic insights in diabetic cardiomyopathy226Effects of miRNAs modulated by endurance training on cardiomyocyte excitability227Differential transcriptome and microRNA expression signatures in the healthy heart (RV vs. LV) and the failing, pressure-overloaded right ventricle (SuHx model)

Author

Costantino, S, primary, Bonzanni, M, primary, Legchenko, E, primary, Paneni, F, additional, Mitchell, K, additional, Berrino, L, additional, Schwarzwald, C, additional, Volpe, M, additional, Luscher, TF, additional, Cosentino, F, additional, Napoli, A, additional, Landi, S, additional, Bucchi, A, additional, Vernillo, G, additional, Baruscotti, M, additional, La Torre, A, additional, Difrancesco, D, additional, Barbuti, A, additional, Kueffner, R, additional, and Hansmann, G, additional

Published
2016
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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

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2016
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7. Poster session 3Cell growth, differentiation and stem cells - Heart511The role of the endocannabinoid system in modelling muscular dystrophy cardiac disease with induced pluripotent stem cells.512An emerging role of T lymphocytes in cardiac regenerative processes in heart failure due to dilated cardiomyopathy513Canonical wnt signaling reverses the ‘aged/senescent’ human endogenous cardiac stem cell phenotype514Hippo signalling modulates survival of human induced pluripotent stem cell-derived cardiomyocytes515Biocompatibility of mesenchymal stem cells with a spider silk matrix and its potential use as scaffold for cardiac tissue regeneration516A snapshot of genome-wide transcription in human induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs)517Can NOS/sGC/cGK1 pathway trigger the differentiation and maturation of mouse embryonic stem cells (ESCs)?518Introduction of external Ik1 to human-induced pluripotent stem cell-derived cardiomyocytes via Ik1-expressing HEK293519Cell therapy of the heart studied using adult myocardial slices in vitro520Enhancement of the paracrine potential of human adipose derived stem cells when cultured as spheroid bodies521Mechanosensitivity of cardiomyocyte progenitor cells: the strain response in 2D and 3D environments522The effect of the vascular-like network on the maturation of the human induced pluripotent stem cell derived cardiomyocytes.Transcriptional control and RNA species - Heart525Gene expression regulation in heart failure: from pathobiology to bioinformatics526Human transcriptome in idiopathic dilated cardiomyopathy - a novel high throughput screening527A high-throghput approach unveils putative miRNA-mediated mitochondria-targeted cardioprotective circuits activated by T3 in the post ischemia reperfusion setting528The effect of uraemia on the expression of miR-212/132 and the calcineurin pathway in the rat heartCytokines and cellular inflammation - Heart531Lack of growth differentiation factor 15 aggravates adverse cardiac remodeling upon pressure-overload in mice532Blocking heteromerization of platelet chemokines ccl5 and cxcl4 reduces inflammation and preserves heart function after myocardial infarction533Is there an association between low-dose aspirin use and clinical outcome in HFPEF? Implications of modulating monocyte function and inflammatory mediator release534N-terminal truncated intracellular matrix metalloproteinase-2 expression in diabetic heart.535Expression of CD39 and CD73 on peripheral T-cell subsets in calcific aortic stenosis536Mast cells in the atrial myocardium of patients with atrial fibrillation: a comparison with patients in sinus rhythm539Characteristics of the inflammatory response in patients with coronary artery disease and arterial hypertension540Pro-inflammatory cytokines as cardiovascular events predictors in rheumatoid arthritis and asymptomatic atherosclerosis541Characterization of FVB/N murinic bone marrow-derived macrophage polarization into M1 and M2 phenotypes542The biological expression and thoracic anterior pain syndromeSignal transduction - Heart545The association of heat shock protein 90 and TGFbeta receptor I is involved in collagen production during cardiac remodelling in aortic-banded mice546Loss of the inhibitory GalphaO protein in the rostral ventrolateral medulla of the brainstem leads to abnormalities in cardiovascular reflexes and altered ventricular excitablitiy547Selenoprotein P regulates pressure overload-induced cardiac remodeling548Study of adenylyl cyclase activity in erythrocyte membranes in patients with chronic heart failure549Direct thrombin inhibitors inhibit atrial myocardium hypertrophy in a rat model of heart failure and atrial remodeling550Tissue factor / FVIIa transactivates the IGF-1R by a Src-dependent phosphorylation of caveolin-1551Notch signaling is differently altered in endothelial and smooth muscle cells of ascending aortic aneurysm patients552Frizzled 5 expression is essential for endothelial proliferation and migration553Modulation of vascular function and ROS production by novel synthetic benzopyran analogues in diabetes mellitusExtracellular matrix and fibrosis - Heart556Cardiac fibroblasts as inflammatory supporter cells trigger cardiac inflammation in heart failure557A role for galectin-3 in calcific aortic valve stenosis558Omega-3 polyunsaturated fatty acids- can they decrease risk for ventricular fibrillation?559Serum levels of elastin derived peptides and circulating elastin-antielastin immune complexes in sera of patients with coronary artery disease560Endocardial fibroelastosis is secondary to hemodynamic alterations in the chick model of hypoplastic left heart syndrome561Dynamics of serum levels of matrix metalloproteinases in primary anterior STEMI patients564Deletion of the alpha-7 nicotinic acetylcholine receptor changes the vascular remodeling induced by transverse aortic constriction in mice.565Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veinsIon channels, ion exchangers and cellular electrophysiology - Heart568Microtubule-associated protein RP/EB family member 1 modulates sodium channel trafficking and cardiac conduction569Investigation of electrophysiological abnormalities in a rabbit athlete's heart model570Upregulation of expression of multiple genes in the atrioventricular node of streptozotocin-induced diabetic rat571miR-1 as a regulator of sinoatrial rhythm in endurance training adaptation572Selective sodium-calcium exchanger inhibition reduces myocardial dysfunction associated with hypokalaemia and ventricular fibrillation573Effect of racemic and levo-methadone on action potential of human ventricular cardiomyocytes574Acute temperature effects on the chick embryonic heart functionVasculogenesis, angiogenesis and arteriogenesis577Clinical improvement and enhanced collateral vessel growth after monocyte transplantation in mice578The role of HIF-1 alpha, VEGF and obstructive sleep apnoea in the development of coronary collateral circulation579Initiating cardiac repair with a trans-coronary sinus catheter intervention in an ischemia/reperfusion porcine animal model580Early adaptation of pre-existing collaterals after acute arteriolar and venular microocclusion: an in vivo study in chick chorioallantoic membraneEndothelium583EDH-type responses to the activator of potassium KCa2.3 and KCa3.1 channels SKA-31 in the small mesenteric artery from spontaneously hypertensive rats584The peculiarities of endothelial dysfunction in patients with chronic renocardial syndrome585Endothelial dysfunction, atherosclerosis of the carotid arteries and level of leptin in patient with coronary heart disease in combination with hepatic steatosis depend from body mass index.586Role of non-coding RNAs in thoracic aortic aneurysm associated with bicuspid aortic valve587Cigarette smoke extract abrogates atheroprotective effects of high laminar flow on endothelial function588The prognostic value of anti-connective tissue antibodies in coronary heart disease and asymptomatic atherosclerosis589Novel potential properties of bioactive peptides from spanish dry-cured ham on the endothelium.Lipids592Intermediate density lipoprotein is associated with monocyte subset distribution in patients with stable atherosclerosis593The characteristics of dyslipidemia in rheumatoid arthritisAtherosclerosis596Macrophages differentiated in vitro are heterogeneous: morphological and functional profile in patients with coronary artery disease597Palmitoylethanolamide promotes anti-inflammatory phenotype of macrophages and attenuates plaque formation in ApoE-/- mice598Amiodarone versus esmolol in the perioperative period: an in vitro study of coronary artery bypass grafts599BMPRII signaling of fibrocytes, a mesenchymal progenitor cell population, is increased in STEMI and dyslipidemia600The characteristics of atherogenesis and systemic inflammation in rheumatoid arthritis601Role of adenosine-to-inosine RNA editing in human atherosclerosis602Presence of bacterial DNA in thrombus aspirates of patients with myocardial infarction603Novel E-selectin binding polymers reduce atherosclerotic lesions in ApoE(-/-) mice604Differential expression of the plasminogen receptor Plg-RKT in monocyte and macrophage subsets - possible functional consequences in atherogenesis605Apelin-13 treatment enhances the stability of atherosclerotic plaques606Mast cells are increased in the media of coronary lesions in patients with myocardial infarction and favor atherosclerotic plaque instability607Association of neutrophil to lymphocyte ratio with presence of isolated coronary artery ectasiaCalcium fluxes and excitation-contraction coupling610The coxsackie- and adenovirus receptor (CAR) regulates calcium homeostasis in the developing heart611HMW-AGEs application acutely reduces ICaL in adult cardiomyocytes612Measuring electrical conductibility of cardiac T-tubular systems613Postnatal development of cardiac excitation-contraction coupling in rats614Role of altered Ca2+ homeostasis during adverse cardiac remodeling after ischemia/reperfusion615Experimental study of sarcoplasmic reticulum dysfunction and energetic metabolism in failing myocardium associated with diabetes mellitusHibernation, stunning and preconditioning618Volatile anesthetic preconditioning attenuates ischemic-reperfusion injury in type II diabetic patients undergoing on-pump heart surgery619The effect of early and delayed phase of remote ischemic preconditioning on ischemia-reperfusion injury in the isolated hearts of healthy and diabetic rats620Post-conditioning with 1668-thioate leads to attenuation of the inflammatory response and remodeling with less fibrosis and better left ventricular function in a murine model of myocardial infarction621Maturation-related changes in response to ischemia-reperfusion injury and in effects of classical ischemic preconditioning and remote preconditioningMitochondria and energetics624Phase changes in myocardial mitochondrial respiration caused by hypoxic preconditioning or periodic hypoxic training625Desmin mutations depress mitochondrial metabolism626Methylene blue modulates mitochondrial function and monoamine oxidases-related ROS production in diabetic rat hearts627Doxorubicin modulates the real-time oxygen consumption rate of freshly isolated adult rat and human ventricular cardiomyocytesCardiomyopathies and fibrosis630Effects of genetic or pharmacologic inhibition of the ubiquitin/proteasome system on myocardial proteostasis and cardiac function631Suppression of Wnt signalling in a desmoglein-2 transgenic mouse model for arrhythmogenic cardiomyopathy632Cold-induced cardiac hypertrophy is reversed after thermo-neutral deacclimatization633CD45 is a sensitive marker to diagnose lymphocytic myocarditis in endomyocardial biopsies of living patients and in autopsies634Atrial epicardial adipose tissue derives from epicardial progenitors635Caloric restriction ameliorates cardiac function, sympathetic cardiac innervation and beta-adrenergic receptor signaling in an experimental model of post-ischemic heart failure636High fat diet improves cardiac remodelling and function after extensive myocardial infarction in mice637Epigenetic therapy reduces cardiac hypertrophy in murine models of heart failure638Imbalance of the VHL/HIF signaling in WT1+ Epicardial Progenitors results in coronary vascular defects, fibrosis and cardiac hypertrophy639Diastolic dysfunction is the first stage of the developing heart failure640Colchicine aggravates coxsackievirus B3 infection in miceArterial and pulmonary hypertension642Osteopontin as a marker of pulmonary hypertension in patients with coronary heart disease combined with chronic obstructive pulmonary disease643Myocardial dynamic stiffness is increased in experimental pulmonary hypertension partly due to incomplete relaxation644Hypotensive effect of quercetin is possibly mediated by down-regulation of immunotroteasome subunits in aorta of spontaneously hypertensive rats645Urocortin-2 improves right ventricular function and attenuates experimental pulmonary arterial hypertension646A preclinical evaluation of the anti-hypertensive properties of an aqueous extract of Agathosma (Buchu)Biomarkers648The adiponectin level in hypertensive females with rheumatoid arthritis and its relationship with subclinical atherosclerosis649Markers for identification of renal dysfunction in the patients with chronic heart failure650cardio-hepatic syndromes in chronic heart failure: North Africa profile651To study other biomarkers that assess during myocardial infarction652Interconnections of apelin levels with parameters of lipid metabolism in hypertension patients653Plasma proteomics in hypertension: prediction and follow-up of albuminuria during chronic renin-angiotensin system suppression654Soluble RAGE levels in plasma of patients with cerebrovascular events

Author

Gowran, A, primary, Kulikova, T, primary, Lewis, FC, primary, Foldes, G, primary, Fuentes, L, primary, Viiri, LE, primary, Spinelli, V, primary, Costa, A, primary, Perbellini, F, primary, Sid-Otmane, C, primary, Bax, NAM, primary, Pekkanen-Mattila, M, primary, Schiano, C, primary, Chaloupka, A, primary, Forini, F, primary, Sarkozy, M, primary, De Jager, SCA, primary, Vajen, T, primary, Glezeva, N, primary, Lee, H W, primary, Golovkin, A, primary, Kucera, T, primary, Musikhina, NA, primary, Korzhenkov, NP, primary, Santuchi, M DE C, primary, Munteanu, D, primary, Garcia, RG, primary, Ang, R, primary, Usui, S, primary, Kamilova, U, primary, Jumeau, C, primary, Aberg, M, primary, Kostina, DA, primary, Brandt, MM, primary, Muntean, D, primary, Lindner, D, primary, Sadaba, R, primary, Bacova, B, primary, Nikolov, A, primary, Sedmera, D, primary, Ryabov, V, primary, Neto, FP, primary, Lynch, M, primary, Portero, V, primary, Kui, P, primary, Howarth, FC, primary, Gualdoni, A, primary, Prorok, J, primary, Diolaiuti, L, primary, Vostarek, F, primary, Wagner, M, primary, Abela, MA, primary, Nebert, C, primary, Xiang, W, primary, Kloza, M, primary, Maslenko, A, primary, Grechanyk, M, primary, Bhattachariya, A, primary, Morawietz, H, primary, Babaeva, AR, primary, Martinez Sanchez, SM, primary, Krychtiuk, KA, primary, Starodubova, J, primary, Fiorelli, S, primary, Rinne, P, primary, Ozkaramanli Gur, D, primary, Hofbauer, T, primary, Stellos, K, primary, Pinon, P, primary, Tsoref, O, primary, Thaler, B, primary, Fraga-Silva, RA, primary, Fuijkschot, WW, primary, Shaaban, MNS, primary, Matthaeus, C, primary, Deluyker, D, primary, Scardigli, M, primary, Zahradnikova, A, primary, Dominguez, A, primary, Kondrat'eva, D, primary, Sosorburam, T, primary, Murarikova, M, primary, Duerr, GD, primary, Griecsova, L, primary, Portnichenko, VI, primary, Smolina, N, primary, Duicu, OANA M, primary, Elder, JM, primary, Zaglia, T, primary, Lorenzon, A, primary, Ruperez, C, primary, Woudstra, L, primary, Suffee, N, primary, De Lucia, C, primary, Russell-Hallinan, A, primary, Menendez-Montes, I, primary, Kapelko, VI, primary, Emmens, RW, primary, Hetman, O, primary, Van Der Laarse, WJ, primary, Goncharov, S, primary, Adao, R, primary, Huisamen, B, primary, Sirenko, O, primary, Nassiri, I, primary, Tserendavaa, SUMIYA, primary, Yushko, K, primary, Baldan Martin, M, primary, Falcone, C, primary, Vigorelli, V, additional, Nigro, P, additional, Pompilio, G, additional, Stepanova, O, additional, Valikhov, M, additional, Samko, A, additional, Masenko, V, additional, Tereschenko, S, additional, Teoh, T, additional, Domenjo-Vila, E, additional, Theologou, T, additional, Field, M, additional, Awad, W, additional, Yasin, M, additional, Nadal-Ginard, B, additional, Ellison-Hughes, GM, additional, Hellen, N, additional, Vittay, O, additional, Harding, SE, additional, Gomez-Cid, L, additional, Fernandez-Santos, ME, additional, Suarez-Sancho, S, additional, Plasencia, V, additional, Climent, A, additional, Sanz-Ruiz, R, additional, Hedhammar, M, additional, Atienza, F, additional, Fernandez-Aviles, F, additional, Kiamehr, M, additional, Oittinen, M, additional, Viiri, KM, additional, Kaikkonen, M, additional, Aalto-Setala, K, additional, Diolaiuti, L, additional, Laurino, A, additional, Sartiani, L, additional, Vona, A, additional, Zanardelli, M, additional, Cerbai, E, additional, Failli, P, additional, Hortigon-Vinagre, MP, additional, Van Der Heyden, M, additional, Burton, FL, additional, Smith, GL, additional, Watson, S, additional, Scigliano, M, additional, Tkach, S, additional, Alayoubi, S, additional, Terracciano, CM, additional, Ly, HQ, additional, Mauretti, A, additional, Van Marion, MH, additional, Van Turnhout, MC, additional, Van Der Schaft, DWJ, additional, Sahlgren, CM, additional, Goumans, MJ, additional, Bouten, CVC, additional, Vuorenpaa, H, additional, Penttinen, K, additional, Sarkanen, R, additional, Ylikomi, T, additional, Heinonen, T, additional, Grimaldi, V, additional, Aprile, M, additional, Esposito, R, additional, Maiello, C, additional, Soricelli, A, additional, Colantuoni, V, additional, Costa, V, additional, Ciccodicola, A, additional, Napoli, C, additional, Rowe, GC, additional, Johnson, K, additional, Arany, ZP, additional, Del Monte, F, additional, D'aurizio, R, additional, Kusmic, C, additional, Nicolini, G, additional, Baumgart, M, additional, Groth, M, additional, Ucciferri, N, additional, Iervasi, G, additional, Pitto, L, additional, Pipicz, M, additional, Gaspar, R, additional, Siska, A, additional, Foldesi, I, additional, Kiss, K, additional, Bencsik, P, additional, Thum, T, additional, Batkai, S, additional, Csont, T, additional, Haan, JJ, additional, Bosch, L, additional, Brans, MAD, additional, Van De Weg, SM, additional, Deddens, JC, additional, Lee, SJ, additional, Sluijter, JPG, additional, Pasterkamp, G, additional, Werner, I, additional, Projahn, D, additional, Staudt, M, additional, Curaj, A, additional, Soenmez, TT, additional, Simsekyilmaz, S, additional, Hackeng, TM, additional, Von Hundelshausen, P, additional, Koenen, RR, additional, Weber, C, additional, Liehn, EA, additional, Santos-Martinez, M, additional, Medina, C, additional, Watson, C, additional, Mcdonald, K, additional, Gilmer, J, additional, Ledwidge, M, additional, Song, SH, additional, Lee, MY, additional, Park, MH, additional, Choi, JC, additional, Ahn, JH, additional, Park, JS, additional, Oh, JH, additional, Choi, JH, additional, Lee, HC, additional, Cha, KS, additional, Hong, TJ, additional, Kudryavtsev, I, additional, Serebryakova, M, additional, Malashicheva, A, additional, Shishkova, A, additional, Zhiduleva, E, additional, Moiseeva, O, additional, Durisova, M, additional, Blaha, M, additional, Melenovsky, V, additional, Pirk, J, additional, Kautzner, J, additional, Petelina, TI, additional, Gapon, LI, additional, Gorbatenko, EA, additional, Potolinskaya, YV, additional, Arkhipova, EV, additional, Solodenkova, KS, additional, Osadchuk, MA, additional, Dutra, MF, additional, Oliveira, FCB, additional, Silva, MM, additional, Passos-Silva, DG, additional, Goncalves, R, additional, Santos, RAS, additional, Da Silva, RF, additional, Gavrilescu, CM, additional, Paraschiv, CM, additional, Manea, P, additional, Strat, LC, additional, Gomez, JMG, additional, Merino, D, additional, Hurle, MA, additional, Nistal, JF, additional, Aires, A, additional, Cortajarena, AL, additional, Villar, AV, additional, Abramowitz, J, additional, Birnbaumer, L, additional, Gourine, AV, additional, Tinker, A, additional, Takamura, M, additional, Takashima, S, additional, Inoue, O, additional, Misu, H, additional, Takamura, T, additional, Kaneko, S, additional, Alieva, TOHIRA, additional, Mougenot, N, additional, Dufilho, M, additional, Hatem, S, additional, Siegbahn, A, additional, Kostina, AS, additional, Uspensky, VE, additional, Moiseeva, OM, additional, Kostareva, AA, additional, Malashicheva, AB, additional, Van Dijk, CGM, additional, Chrifi, I, additional, Verhaar, MC, additional, Duncker, DJ, additional, Cheng, C, additional, Sturza, A, additional, Petrus, A, additional, Duicu, O, additional, Kiss, L, additional, Danila, M, additional, Baczko, I, additional, Jost, N, additional, Gotzhein, F, additional, Schon, J, additional, Schwarzl, M, additional, Hinrichs, S, additional, Blankenberg, S, additional, Volker, U, additional, Hammer, E, additional, Westermann, D, additional, Martinez-Martinez, E, additional, Arrieta, V, additional, Fernandez-Celis, A, additional, Jimenez-Alfaro, L, additional, Melero, A, additional, Alvarez-Asiain, V, additional, Cachofeiro, V, additional, Lopez-Andres, N, additional, Tribulova, N, additional, Wallukat, G, additional, Knezl, V, additional, Radosinska, J, additional, Barancik, M, additional, Tsinlikov, I, additional, Tsinlikova, I, additional, Nicoloff, G, additional, Blazhev, A, additional, Pesevski, Z, additional, Kvasilova, A, additional, Stopkova, T, additional, Eckhardt, A, additional, Buffinton, C M, additional, Nanka, O, additional, Kercheva, M, additional, Suslova, T, additional, Gusakova, A, additional, Ryabova, T, additional, Markov, V, additional, Karpov, R, additional, Seemann, H, additional, Alcantara, TC, additional, Santuchi, M DE C, additional, Fonseca, SG, additional, Barallobre-Barreiro, J, additional, Oklu, R, additional, Fava, M, additional, Baig, F, additional, Yin, X, additional, Albadawi, H, additional, Jahangiri, M, additional, Stoughton, J, additional, Mayr, M, additional, Podliesna, SP, additional, Veerman, CCV, additional, Verkerk, AOV, additional, Klerk, MK, additional, Lodder, EML, additional, Mengarelli, IM, additional, Bezzina, CRB, additional, Remme, CAR, additional, Takacs, H, additional, Polyak, A, additional, Morvay, N, additional, Lepran, I, additional, Tiszlavicz, L, additional, Nagy, N, additional, Ordog, B, additional, Farkas, A, additional, Forster, T, additional, Varro, A, additional, Farkas, AS, additional, Jayaprakash, P, additional, Parekh, K, additional, Ferdous, Z, additional, Oz, M, additional, Dobrzynski, H, additional, Adrian, TE, additional, Landi, S, additional, Bonzanni, M, additional, D'souza, A, additional, Boyett, M, additional, Bucchi, A, additional, Baruscotti, M, additional, Difrancesco, D, additional, Barbuti, A, additional, Kui, P, additional, Oravecz, K, additional, Hezso, T, additional, Levijoki, J, additional, Pollesello, P, additional, Koskelainen, T, additional, Otsomaa, L, additional, Farkas, A S, additional, Papp, JGY, additional, Toth, A, additional, Acsai, K, additional, Dini, L, additional, Mazzoni, L, additional, Mugelli, A, additional, Svatunkova, J, additional, Sedmera, D, additional, Deffge, C, additional, Baer, C, additional, Weinert, S, additional, Braun-Dullaeus, RC, additional, Herold, J, additional, Cassar, AC, additional, Zahra, GZ, additional, Pllaha, EP, additional, Dingli, PD, additional, Montefort, SM, additional, Xuereb, RGX, additional, Aschacher, T, additional, Messner, B, additional, Eichmair, E, additional, Mohl, W, additional, Reglin, B, additional, Rong, W, additional, Nitzsche, B, additional, Maibier, M, additional, Guimaraes, P, additional, Ruggeri, A, additional, Secomb, TW, additional, Pries, AR, additional, Baranowska-Kuczko, M, additional, Karpinska, O, additional, Kusaczuk, M, additional, Malinowska, B, additional, Kozlowska, H, additional, Demikhova, N, additional, Vynnychenko, L, additional, Prykhodko, O, additional, Grechanyk, N, additional, Kuryata, A, additional, Cottrill, KA, additional, Du, L, additional, Bjorck, HM, additional, Maleki, S, additional, Franco-Cereceda, A, additional, Chan, SY, additional, Eriksson, P, additional, Giebe, S, additional, Cockcroft, N, additional, Hewitt, K, additional, Brux, M, additional, Brunssen, C, additional, Tarasov, AA, additional, Davidov, SI, additional, Reznikova, EA, additional, Tapia Abellan, A, additional, Angosto Bazarra, D, additional, Pelegrin Vivancos, P, additional, Montoro Garcia, S, additional, Kastl, SP, additional, Pongratz, T, additional, Goliasch, G, additional, Gaspar, L, additional, Maurer, G, additional, Huber, K, additional, Dostal, E, additional, Pfaffenberger, S, additional, Oravec, S, additional, Wojta, J, additional, Speidl, WS, additional, Osipova, I, additional, Sopotova, I, additional, Eligini, S, additional, Cosentino, N, additional, Marenzi, G, additional, Tremoli, E, additional, Rami, M, additional, Ring, L, additional, Steffens, S, additional, Gur, O, additional, Gurkan, S, additional, Mangold, A, additional, Scherz, T, additional, Panzenboeck, A, additional, Staier, N, additional, Heidari, H, additional, Mueller, J, additional, Lang, IM, additional, Gatsiou, A, additional, Stamatelopoulos, K, additional, Perisic, L, additional, John, D, additional, Lunella, FF, additional, Hedin, U, additional, Zeiher, A, additional, Dimmeler, S, additional, Nunez, L, additional, Moure, R, additional, Marron-Linares, G, additional, Flores, X, additional, Aldama, G, additional, Salgado, J, additional, Calvino, R, additional, Tomas, M, additional, Bou, G, additional, Vazquez, N, additional, Hermida-Prieto, M, additional, Vazquez-Rodriguez, JM, additional, Amit, U, additional, Landa, N, additional, Kain, D, additional, Tyomkin, D, additional, David, A, additional, Leor, J, additional, Hohensinner, PJ, additional, Baumgartner, J, additional, Krychtiuk, KA, additional, Baik, N, additional, Miles, LA, additional, Seeman, H, additional, Montecucco, F, additional, Da Silva, AR, additional, Costa-Fraga, FP, additional, Anguenot, L, additional, Mach, FP, additional, Stergiopulos, N, additional, Kupreishvili, K, additional, Vonk, ABA, additional, Smulders, YM, additional, Van Hinsbergh, VWM, additional, Stooker, W, additional, Niessen, HWM, additional, Krijnen, PAJ, additional, Ashmawy, MM, additional, Salama, MA, additional, Elamrosy, MZ, additional, Juettner, R, additional, Rathjen, F G, additional, Bito, V, additional, Crocini, C, additional, Ferrantini, C, additional, Gabbrielli, T, additional, Silvestri, L, additional, Coppini, R, additional, Tesi, C, additional, Poggesi, C, additional, Pavone, FS, additional, Sacconi, L, additional, Mackova, K, additional, Zahradnik, I, additional, Zahradnikova, A, additional, Diaz, I, additional, Sanchez De Rojas De Pedro, E, additional, Hmadcha, K, additional, Calderon Sanchez, E, additional, Benitah, JP, additional, Gomez, AM, additional, Smani, T, additional, Ordonez, A, additional, Afanasiev, SA, additional, Egorova, MV, additional, Popov, SV, additional, Wu Qing, P, additional, Cheng, X, additional, Carnicka, S, additional, Pancza, D, additional, Jasova, M, additional, Kancirova, I, additional, Ferko, M, additional, Ravingerova, T, additional, Wu, S, additional, Schneider, M, additional, Marggraf, V, additional, Verfuerth, L, additional, Frede, S, additional, Boehm, O, additional, Dewald, O, additional, Baumgarten, G, additional, Kim, S-C, additional, Farkasova, V, additional, Gablovsky, I, additional, Bernatova, I, additional, Nosar, V, additional, Portnychenko, A, additional, Drevytska, T, additional, Mankovska, I, additional, Gogvadze, V, additional, Sejersen, T, additional, Kostareva, A, additional, Wolf, A, additional, Privistirescu, A, additional, Muntean, D, additional, O ' Gara, P, additional, Sanchez-Alonso, JL, additional, Lyon, AR, additional, Prando, V, additional, Pianca, N, additional, Lo Verso, F, additional, Milan, G, additional, Pesce, P, additional, Sandri, M, additional, Mongillo, M, additional, Beffagna, G, additional, Poloni, G, additional, Dazzo, E, additional, Sabatelli, P, additional, Doliana, R, additional, Polishchuk, R, additional, Carnevale, D, additional, Lembo, G, additional, Bonaldo, P, additional, Braghetta, P, additional, Rampazzo, A, additional, Cairo, M, additional, Giralt, M, additional, Villarroya, F, additional, Planavila, A, additional, Biesbroek, PS, additional, Emmens, RWE, additional, Juffermans, LJM, additional, Van Der Wall, AC, additional, Van Rossum, AC, additional, Niessen, JWM, additional, Moor Morris, T, additional, Dilanian, G, additional, Farahmand, P, additional, Puceat, M, additional, Gambino, G, additional, Petraglia, L, additional, Elia, A, additional, Komici, K, additional, Femminella, GD, additional, D'amico, ML, additional, Pagano, G, additional, Cannavo, A, additional, Liccardo, D, additional, Koch, WJ, additional, Nolano, M, additional, Leosco, D, additional, Ferrara, N, additional, Rengo, G, additional, Neary, R, additional, Shiels, L, additional, Baugh, J, additional, Palacios, B, additional, Escobar, B, additional, Alonso, AV, additional, Guzman, G, additional, Ruiz-Cabello, J, additional, Jimenez-Borreguero, LJ, additional, Martin-Puig, S, additional, Lakomkin, VL, additional, Lukoshkova, EV, additional, Abramov, AA, additional, Gramovich, VV, additional, Vyborov, ON, additional, Ermishkin, VV, additional, Undrovinas, NA, additional, Shirinsky, VP, additional, Smilde, BJ, additional, Woudstra, L, additional, Fong Hing, G, additional, Wouters, D, additional, Zeerleder, S, additional, Murk, JL, additional, Van Ham, SM, additional, Heymans, S, additional, Krakhmalova, O, additional, Van Groen, D, additional, Bogaards, SJP, additional, Schalij, I, additional, Portnichenko, GV, additional, Tumanovska, LV, additional, Goshovska, YV, additional, Lapikova-Bryhinska, TU, additional, Nagibin, VS, additional, Dosenko, VE, additional, Mendes-Ferreira, P, additional, Maia-Rocha, C, additional, Santos-Ribeiro, D, additional, Potus, F, additional, Breuils-Bonnet, S, additional, Provencher, S, additional, Bonnet, S, additional, Rademaker, M, additional, Leite-Moreira, AF, additional, Bras-Silva, C, additional, Lopes, J, additional, Kuryata, O, additional, Lusynets, T, additional, Alikulov, I, additional, Nourddine, M, additional, Azzouzi, L, additional, Habbal, R, additional, Tserendavaa, SUMIYA, additional, Enkhtaivan, ODKHUU, additional, Shagdar, ZORIGO, additional, Malchinkhuu, MUNKHZ, additional, Malchinkhuu, MUNLHZ, additional, Koval, S, additional, Starchenko, T, additional, Mourino-Alvarez, L, additional, Gonzalez-Calero, L, additional, Sastre-Oliva, T, additional, Lopez, JA, additional, Vazquez, J, additional, Alvarez-Llamas, G, additional, Ruilope, LUIS M, additional, De La Cuesta, F, additional, Barderas, MG, additional, Bozzini, S, additional, D'angelo, A, additional, and Pelissero, G, additional

Published
2016
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11. The expression of the rare caveolin-3 variant T78M alters cardiac ion channels function and membrane excitability

Author

Mirko Baruscotti, Elena Vezzoli, Dario DiFrancesco, Giulia Campostrini, Lia Crotti, Alessio Lissoni, Maura Francolini, Peter J. Schwartz, Claudia Bazzini, Riccardo Cappato, Annalisa Bucchi, Stefano Severi, Matteo Fantini, Mattia Bonzanni, Andrea Barbuti, Ilaria Rivolta, Raffaella Milanesi, Campostrini, Giulia, Bonzanni, Mattia, Lissoni, Alessio, Bazzini, Claudia, Milanesi, Raffaella, Vezzoli, Elena, Francolini, Maura, Baruscotti, Mirko, Bucchi, Annalisa, Rivolta, Ilaria, Fantini, Matteo, Severi, Stefano, Cappato, Riccardo, Crotti, Lia, Schwartz, Peter J., DiFrancesco, Dario, Barbuti, Andrea, Campostrini, G, Bonzanni, M, Lissoni, A, Bazzini, C, Milanesi, R, Vezzoli, E, Francolini, M, Baruscotti, M, Bucchi, A, Rivolta, I, Fantini, M, Severi, S, Cappato, R, Crotti, L, Schwartz, P, Di Francesco, D, and Barbuti, A

Subjects
0301 basic medicine, Potassium Channels, Caveolin 3, Physiology, Caveolin 1, Genetic disease, PROTEIN, Action Potentials, Muscle Proteins, 030204 cardiovascular system & hematology, Rats, Sprague-Dawley, Mice, 0302 clinical medicine, BIO/09 - FISIOLOGIA, EXOME DATA, Heart Rate, Caveolin, Medicine and Health Sciences, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Myocyte, Myocytes, Cardiac, Mice, Knockout, Models, Cardiovascular, LOCALIZATION, 3T3 Cells, Electrophysiology, Ion channels, cardiovascular system, Ion Channels and Arrhythmias, Ion channel, Cardiology and Cardiovascular Medicine, Ion Channel Gating, Arrhythmia, Genetic diseases, LONG-QT SYNDROME, Biology, MYOCYTES, Caveolae, Transfection, LATE SODIUM CURRENT, Kv1.5 Potassium Channel, 03 medical and health sciences, Physiology (medical), INFANT-DEATH-SYNDROME, Animals, Humans, HCN4, Computer Simulation, Transcription factor, MUTATIONS, Cardiac arrhythmia, Arrhythmias, Cardiac, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Original Articles, Fibroblasts, Myocardial Contraction, CHRONIC ATRIAL-FIBRILLATION, Kinetics, 030104 developmental biology, Membrane protein, Mutation, Neuroscience
Abstract

The identification of new molecular insights always drove the research. Data from genetic, molecular biology and biochemistry suggest new directions, open new fields and lead to new discoveries. The significance of these data is, in certain situation, difficult to envision. In this view, physiology could represent one of the possible read-out of the overall complex modifications inside the cell. In particular, electrophysiological analysis shed light on both physiological and pathological conditions in excitable and non-excitable cells. In excitable cell, ion channels, cellular microenvironment, transcription factors and accessory proteins shape the electric profile of the cell. In my PhD, I mainly used this approach to test the effect of mutations associated with arrhythmic diseases (in both cardiac arrhythmia and epilepsy) and of physiopathological remodeling in response to endurance training. In particular, I performed the following projects concerning: - Characterization of the biophysical properties of the hHCN1 L157V mutation found in a patient affected by idiopathic generalized epilepsy. This mutation resulted to decrease the current density and leading to an increased excitability in single neonatal rat cortical neurons. - Analysis of the cardiac endurance training-associated microRNAs (miRNAs) in a trained mouse model and of the role of the muscle-specific miRNAs in modulating membrane excitability in the neonatal rat ventricular cardiomyocytes. These results highlights new miRNAs potentially involved in the cardiac electrical remodeling associated with endurance training. - Characterization of the impact of the T78M cav-3 variant found in a cohort of arrhythmic patients. This variant induces modification of several ionic currents leading to a pro-arrhythmogenic profile. The leitmotiv of these projects is the identification of the causes underlying the pathophysiological modification of excitable cells by ion channels, membrane proteins and post-transcriptional molecules.

Published
2017

12. A Loss-of-Function HCN4 Mutation Associated With Familial Benign Myoclonic Epilepsy in Infancy Causes Increased Neuronal Excitability

Author

Giulia Campostrini, Jacopo C. DiFrancesco, Barbara Castellotti, Raffaella Milanesi, Tomaso Gnecchi-Ruscone, Mattia Bonzanni, Annalisa Bucchi, Mirko Baruscotti, Carlo Ferrarese, Silvana Franceschetti, Laura Canafoglia, Francesca Ragona, Elena Freri, Angelo Labate, Antonio Gambardella, Cinzia Costa, Cinzia Gellera, Tiziana Granata, Andrea Barbuti, Dario DiFrancesco, Campostrini, G, Difrancesco, J, Castellotti, B, Milanesi, R, Gnecchi-Ruscone, T, Bonzanni, M, Bucchi, A, Baruscotti, M, Ferrarese, C, Franceschetti, S, Canafoglia, L, Ragona, F, Freri, E, Labate, A, Gambardella, A, Costa, C, Gellera, C, Granata, T, Barbuti, A, and Difrancesco, D

Subjects
0301 basic medicine, Bradycardia, Gene isoform, Mutant, medicine.disease_cause, Epilepsy, HCN4, Ion channels, Myoclonic epilepsy of infancy, Neuronal excitability, Molecular Biology, Cellular and Molecular Neuroscience, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, medicine, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Loss function, Mutation, business.industry, medicine.disease, 030104 developmental biology, Etiology, Myoclonic epilepsy, medicine.symptom, Ion channel, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

HCN channels are highly expressed and functionally relevant in neurons and increasing evidence demonstrates their involvement in the etiology of human epilepsies. Among HCN isoforms, HCN4 is important in cardiac tissue, where it underlies pacemaker activity. Despite being expressed also in deep structures of the brain, mutations of this channel functionally shown to be associated with epilepsy have not been reported yet. Using Next Generation Sequencing for the screening of patients with idiopathic epilepsy, we identified the p.Arg550Cys (c.1648C>T) heterozygous mutation on HCN4 in two brothers affected by benign myoclonic epilepsy of infancy. Functional characterization in heterologous expression system and in neurons showed that the mutation determines a loss of function of HCN4 contribution to activity and an increase of neuronal discharge, potentially predisposing to epilepsy. Expressed in cardiomyocytes, mutant channels activate at slightly more negative voltages than wild-type (WT), in accordance with borderline bradycardia. While HCN4 variants have been frequently associated with cardiac arrhythmias, these data represent the first experimental evidence that functional alteration of HCN4 can also be involved in human epilepsy through a loss-of-function effect and associated increased neuronal excitability. Since HCN4 appears to be highly expressed in deep brain structures only early during development, our data provide a potential explanation for a link between dysfunctional HCN4 and infantile epilepsy. These findings suggest that it may be useful to include HCN4 screening to extend the knowledge of the genetic causes of infantile epilepsies, potentially paving the way for the identification of innovative therapeutic strategies.

Published
2018

13. Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knock in mouse model of Alzheimer's disease.

Author

Bonzanni M, Braga A, Saito T, Saido TC, Tesco G, and Haydon PG

Abstract

The disease's trajectory of Alzheimer's disease (AD) is associated with and worsened by hippocampal hyperexcitability. Here we show that during the asymptomatic stage in a knock in mouse model of Alzheimer's disease (APP NL-G-F/NL-G-F ; APPKI), hippocampal hyperactivity occurs at the synaptic compartment, propagates to the soma and is manifesting at low frequencies of stimulation. We show that this aberrant excitability is associated with a deficient adenosine tone, an inhibitory neuromodulator, driven by reduced levels of CD39/73 enzymes, responsible for the extracellular ATP-to-adenosine conversion. Both pharmacologic (adenosine kinase inhibitor) and non-pharmacologic (ketogenic diet) restorations of the adenosine tone successfully normalize hippocampal neuronal activity. Our results demonstrated that neuronal hyperexcitability during the asymptomatic stage of a KI model of Alzheimer's disease originated at the synaptic compartment and is associated with adenosine deficient tone. These results extend our comprehension of the hippocampal vulnerability associated with the asymptomatic stage of Alzheimer's disease., Competing Interests: Declaration of interests Nothing to declare.

Published
2024
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14. Impact of Membrane Voltage on Formation and Stability of Human Renal Proximal Tubules in Vitro .

Author

Adelfio M, Bonzanni M, Levin M, and Kaplan DL

Subjects
Adenosine Triphosphate metabolism, Female, Humans, Kidney, Male, Tissue Engineering methods, Kidney Tubules, Proximal metabolism, Renal Insufficiency, Chronic metabolism
Abstract

More than 15% of adults in the United States suffer from some form of chronic kidney disease (CKD). Current strategies for CKD consist of dialysis or kidney transplant, which, however, can take several years. In this light, tissue engineering and regenerative medicine approaches are the key to improving people's living conditions by advancing previous tissue engineering approaches and seeking new targets as intervention methods for kidney repair or replacement. The membrane voltage ( V m ) dynamics of a cell have been associated with cell migration, cell cycle progression, differentiation, and pattern formation. Furthermore, bioelectrical stimuli have been used as a means in the treatment of diseases and wound healing. Here, we investigated the role of V m as a novel target to guide and manipulate in vitro renal tissue models. Human-immortalized renal proximal tubule epithelial cells (RPTECs-TERT1) were cultured on Matrigel to support the formation of 3D proximal tubular-like structures with the incorporation of a voltage-sensitive dye indicator─bis-(1,3-dibutylbarbituric acid)timethine oxonol (DiBAC). The results demonstrated a correlation between the depolarization and the reorganization of human renal proximal tubule cells, indicating V m as a candidate variable to control these events. Accordingly, V m was pharmacologically manipulated using glibenclamide and pinacidil, K ATP channel modulators, and proximal tubule formation and tubule stability over 21 days were assessed. Chronic manipulation of K ATP channels induced changes in the tubular network topology without affecting lumen formation. Thus, a relationship was found between the preluminal tubulogenesis phase and K ATP channels. This relationship may provide future options as a control point during kidney tissue development, treatment, and regeneration goals.

Published
2022
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15. On the prediction of neuronal microscale topology descriptors based on mesoscale recordings.

Author

Bonzanni M and Kaplan DL

Subjects
Cluster Analysis, Computer Simulation, Brain, Neurons
Abstract

The brain possesses structural and functional hierarchical architectures organized over multiple scales. Considering that functional recordings commonly focused on a single spatial level, and because multiple scales interact with one another, we explored the behaviour of in silico neuronal networks across different scales. We established ad hoc relations of several topological descriptors (average clustering coefficient, average path length, small-world propensity, modularity, network degree, synchronizability and fraction of long-term connections) between different scales upon application and empirical validation of a Euclidian renormalization approach. We tested a simple network (distance-dependent model) as well as an artificial cortical network (Vertex; undirected and directed networks) finding the same qualitative power law relations of the parameters across levels: their quantitative nature is model dependent. Those findings were then organized in a workflow that can be used to predict, with approximation, microscale topologies from mesoscale recordings. The present manuscript not only presents a theoretical framework for the renormalization of biological neuronal network and their study across scales in light of the spatial features of the recording method but also proposes an applicable workflow to compare real functional networks across scales., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Published
2021
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16. Integrated functional neuronal network analysis of 3D silk-collagen scaffold-based mouse cortical culture.

Author

Dingle YL, Bonzanni M, Liaudanskaya V, Nieland TJF, and Kaplan DL

Subjects
Animals, Cell Culture Techniques, Cell Differentiation, Cerebral Cortex cytology, Mice, Nerve Net cytology, Neurons cytology, Cerebral Cortex metabolism, Collagen chemistry, Nerve Net metabolism, Neural Networks, Computer, Neurons metabolism, Silk chemistry, Tissue Scaffolds chemistry
Abstract

Bioengineered 3D tunable neuronal constructs are a versatile platform for studying neuronal network functions, offering numerous advantages over existing technologies and providing for the discovery of new biological insights. Functional neural networks can be evaluated using calcium imaging and quantitatively described using network science. This protocol includes instructions for fabricating protein-based composite scaffolds, 3D in vitro culture of embryonic mouse cortical neurons, virally induced expression of GCaMP6f, wide-field calcium imaging, and computational analysis with open-source software and custom MATLAB code. For complete details on the use and execution of this protocol, please refer to Dingle et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Published
2021
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17. On the effect of neuronal spatial subsampling in small-world networks.

Author

Bonzanni M, Bockley KM, and Kaplan DL

Subjects
Cluster Analysis, Computer Simulation, Neurons
Abstract

The analysis of real-world networks of neurons is biased by the current ability to measure just a subsample of the entire network. It is thus relevant to understand if the information gained in the subsamples can be extended to the global network to improve functional interpretations. Here we showed how average clustering coefficient (CC), average path length (PL), and small-world propensity (SWP) scale when spatial sampling is applied to small-world networks. This extraction mimics the measurement of physical neighbors by means of electrical and optical techniques, both used to study neuronal networks. We applied this method to in silico and in vivo data and we found that the analyzed properties scale with the size of the sampled network and the global network topology. By means of mathematical manipulations, the topology dependence was reduced during scaling. We highlighted the behaviors of the descriptors that, qualitatively, are shared by all the analyzed networks and that allowed an approximated prediction of those descriptors in the global graph using the subgraph information. In contrast, below a spatial threshold, any extrapolation failed; the subgraphs no longer contain enough information to make predictions. In conclusion, the size of the chosen subgraphs is critical to extend the findings to the global network., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Published
2021
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18. The effects of membrane potential and extracellular matrix composition on vascular differentiation of cardiac progenitor cells.

Author

Daley MC, Bonzanni M, MacKenzie AM, Kaplan DL, and Black LD 3rd

Subjects
Animals, Cells, Cultured, Extracellular Matrix drug effects, Humans, Membrane Potentials drug effects, Myocytes, Cardiac drug effects, Myocytes, Smooth Muscle drug effects, Stem Cells drug effects, Swine, Tissue Engineering methods, Tissue Scaffolds chemistry, Cell Differentiation drug effects, Extracellular Matrix chemistry, Myocytes, Cardiac cytology, Myocytes, Smooth Muscle cytology, Stem Cells cytology
Abstract

Historically, the field of tissue engineering has been adept at modulating the chemical and physical microenvironment. This approach has yielded significant progress, but it is imperative to further integrate our understanding of other fundamental cell signaling paradigms into tissue engineering methods. Bioelectric signaling has been demonstrated to be a vital part of tissue development, regeneration, and function across organ systems and the extracellular matrix is known to alter the bioelectric properties of cells. Thus, there is a need to bolster our understanding of how matrix and bioelectric signals interact to drive cell phenotype. We examine how cardiac progenitor cell differentiation is altered by simultaneous changes in both resting membrane potential and extracellular matrix composition. Pediatric c-kit + cardiac progenitor cells were differentiated on fetal or adult cardiac extracellular matrix while being treated with drugs that alter resting membrane potential. Smooth muscle gene expression was increased with depolarization and decreased with hyperpolarization while endothelial and cardiac expression were unchanged. Early smooth muscle protein expression is modified by matrix developmental age, with fetal ECM appearing to amplify the effects of resting membrane potential. Thus, combining matrix composition and bioelectric signaling represents a potential alternative for guiding cell behavior in tissue engineering and regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
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19. A 3D Tissue Model of Traumatic Brain Injury with Excitotoxicity That Is Inhibited by Chronic Exposure to Gabapentinoids.

Author

Rouleau N, Bonzanni M, Erndt-Marino JD, Sievert K, Ramirez CG, Rusk W, Levin M, and Kaplan DL

Subjects
Bioengineering, Brain Injuries, Traumatic drug therapy, Brain Injuries, Traumatic genetics, Brain Injuries, Traumatic metabolism, Cell Death, Gabapentin therapeutic use, Humans, Models, Biological, Phenotype, Brain Injuries, Traumatic pathology, Gabapentin pharmacology, Glutamic Acid metabolism, Tissue Engineering methods
Abstract

Injury progression associated with cerebral laceration is insidious. Following the initial trauma, brain tissues become hyperexcitable, begetting further damage that compounds the initial impact over time. Clinicians have adopted several strategies to mitigate the effects of secondary brain injury; however, higher throughput screening tools with modular flexibility are needed to expedite mechanistic studies and drug discovery that will contribute to the enhanced protection, repair, and even the regeneration of neural tissues. Here we present a novel bioengineered cortical brain model of traumatic brain injury (TBI) that displays characteristics of primary and secondary injury, including an outwardly radiating cell death phenotype and increased glutamate release with excitotoxic features. DNA content and tissue function were normalized by high-concentration, chronic administrations of gabapentinoids. Additional experiments suggested that the treatment effects were likely neuroprotective rather than regenerative, as evidenced by the drug-mediated decreases in cell excitability and an absence of drug-induced proliferation. We conclude that the present model of traumatic brain injury demonstrates validity and can serve as a customizable experimental platform to assess the individual contribution of cell types on TBI progression, as well as to screen anti-excitotoxic and pro-regenerative compounds.

Published
2020
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20. Optogenetically induced cellular habituation in non-neuronal cells.

Author

Bonzanni M, Rouleau N, Levin M, and Kaplan DL

Subjects
Epithelial Cells cytology, Epithelial Cells radiation effects, HEK293 Cells, Humans, Membrane Potentials, Potassium Channels metabolism, Epithelial Cells metabolism, Habituation, Psychophysiologic, Optogenetics methods
Abstract

Habituation, defined as the reversible decrement of a response during repetitive stimulation, is widely established as a form of non-associative learning. Though more commonly ascribed to neural cells and systems, habituation has also been observed in single aneural cells, although evidence is limited. Considering the generalizability of the habituation process, we tested the degree to which organism-level behavioral and single cell manifestations were similar. Human embryonic kidney (HEK) cells that overexpressed an optogenetic actuator were photostimulated to test the effect of different stimulation protocols on cell responses. Depolarization induced by the photocurrent decreased successively over the stimulation protocol and the effect was reversible upon withdrawal of the stimulus. In addition to frequency- and intensity-dependent effects, the history of stimulations on the cells impacted subsequent depolarization in response to further stimulation. We identified tetraethylammonium (TEA)-sensitive native K+ channels as one of the mediators of this habituation phenotype. Finally, we used a theoretical model of habituation to elucidate some mechanistic aspects of the habituation response. In conclusion, we affirm that habituation is a time- and state-dependent biological strategy that can be adopted also by individual non-neuronal cells in response to repetitive stimuli., Competing Interests: The authors have declared that no competing interests exist.

Published
2020
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21. Defined extracellular ionic solutions to study and manipulate the cellular resting membrane potential.

Author

Bonzanni M, Payne SL, Adelfio M, Kaplan DL, Levin M, and Oudin MJ

Subjects
Algorithms, Biological Transport, Cell Membrane metabolism, Cell Membrane Permeability, Electrophysiological Phenomena, Epithelial Cells, Extracellular Space metabolism, Humans, Ions chemistry, Models, Theoretical, Patch-Clamp Techniques, Solutions, Ions metabolism, Membrane Potentials physiology
Abstract

All cells possess an electric potential across their plasma membranes and can generate and receive bioelectric signals. The cellular resting membrane potential (RMP) can regulate cell proliferation, differentiation and apoptosis. Current approaches to measure the RMP rely on patch clamping, which is technically challenging, low-throughput and not widely available. It is therefore critical to develop simple strategies to measure, manipulate and characterize the RMP. Here, we present a simple methodology to study the RMP of non-excitable cells and characterize the contribution of individual ions to the RMP using a voltage-sensitive dye. We define protocols using extracellular solutions in which permeable ions (Na + , Cl - and K + ) are substituted with non-permeable ions [N-Methyl-D-glucamine (NMDG), gluconate, choline, SO 4 2- ]. The resulting RMP modifications were assessed with both patch clamp and a voltage sensitive dye. Using an epithelial and cancer cell line, we demonstrate that the proposed ionic solutions can selectively modify the RMP and help determine the relative contribution of ionic species in setting the RMP. The proposed method is simple and reproducible and will make the study of bioelectricity more readily available to the cell biology community.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Published
2020
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22. Hyperosmolar potassium inhibits myofibroblast conversion and reduces scar tissue formation.

Author

Grasman JM, Williams MD, Razis CG, Bonzanni M, Golding AS, Cairns DM, Levin M, and Kaplan DL

Abstract

Scar formation is a natural result of almost all wound healing in adult mammals. Unfortunately, scarring disrupts normal tissue function and can cause significant physical and psychological distress. In addition to improving surgical techniques to limit scar formation, several therapies are under development towards the same goal. Many of these treatments aim to disrupt transforming growth factor β1 (TGFβ1) signaling, as this is a critical control point for fibroblast differentiation into myofibroblasts; a contractile cell that organizes synthesized collagen fibrils into scar tissue. The present study aimed to examine the role of hyperosmolar potassium gluconate (KGluc) on fibroblast function in skin repair. KGluc was first determined to negatively regulate fibroblast proliferation, metabolism, and migration in a dose-dependent manner in vitro . Increasing concentrations of KGluc also inhibited differentiation into myofibroblasts, suggesting that local KGluc treatment might reduce fibrosis. KGluc delivery was confirmed via loading into collagen hydrogels and used to treat a full thickness skin wound in mice. KGluc qualitatively slowed initial closure of the wounds and resulted in tissue that more closely resembled mature, healthy skin (epidermal thickness and dermal-epidermal morphology) when compared to unloaded collagen hydrogels. KGluc treatment significantly reduced the number of myofibroblasts within the dermis while upregulated blood vessel density with respect to unloaded hydrogels, likely a result of disruption of TGFβ1 signaling. Taken together, these data demonstrate the effectiveness of KGluc treatment on skin wound healing and suggest that this may be an efficient treatment to limit scar formation., Competing Interests: COMPETING INTERESTS The authors declare no competing financial or non-financial interests.

Published
2019
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23. On the Generalization of Habituation: How Discrete Biological Systems Respond to Repetitive Stimuli: A Novel Model of Habituation That Is Independent of Any Biological System.

Author

Bonzanni M, Rouleau N, Levin M, and Kaplan DL

Subjects
Animals, Humans, Nervous System, Neuronal Plasticity physiology, Neurons physiology, Habituation, Psychophysiologic physiology, Nervous System Physiological Phenomena
Abstract

Habituation, a form of non-associative learning, isno longer studied exclusively within the fields of psychology and neuroscience. Indeed, the same stimulus-response pattern is observed at the molecular, cellular, and organismal scales and is not dependent upon the presence of neurons. Hence, a more inclusive theory is required to accommodate aneural forms of habituation. Here an abstraction of the habituation process that does not rely upon particular biological pathways or substrates is presented. Instead, five generalizable elements that define the habituation process are operationalized. The formulation can be applied to interrogate systems as they respond to several stimulation paradigms, providing new insights and supporting existing behavioral data. The model can be used to deduce the relative contribution of elements that contribute to the measurable output of the system. The results suggest that habituation serves as a general biological strategy that any system can implement to adaptively respond to harmless, repetitive stimuli., (© 2019 The Authors. BioEssays Published by Wiley Periodicals, Inc.)

Published
2019
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24. Functional Effects of a Neuromelanin Analogue on Dopaminergic Neurons in 3D Cell Culture.

Author

Collins W, Rouleau N, Bonzanni M, Kapner K, Jeremiah A, Du C, Pothos EN, and Kaplan DL

Abstract

The substantia nigra pars compacta (SNpc) is a discrete region of the brain that exhibits a dark pigment, neuromelanin (NM), a biomaterial with unique properties and the subject of ongoing research pertaining to neurodegenerative conditions like Parkinson's disease (PD). Obtaining human tissue to isolate this pigment is costly and labor intensive, making it necessary to find alternatives to model the biochemical interaction of NM and its implications on PD. To address this limitation, we modified our established silk 3D brain tissue model to emulate key characteristics of the SNpc by using a structural analogue of NM to examine the effects of the material on dopaminergic neurons using Lund's human mesencephalon (LUHMES) cells. We utilized a sepia-melanin, squid ink, derived NM analogue (NM-sim) to chelate ferric iron, and this iron-neuromelanin precipitate (Fe-NM) was purified and characterized. We then exposed LUHMES dopaminergic cells to the NM-sim, Fe-NM-sim, and control vehicle within 3D silk protein scaffolds. The presence of both NM-sim and Fe-NM-sim in the scaffolds negatively impacted spontaneous electrical activity from the LUMES networks, as evidenced by changes in local field potential (LFP) electrophysiological recordings. Furthermore, the Fe-NM-sim precipitate generated peroxides, depleted nutrients/antioxidants, and increased protein oxidation by carbonylation in sustained (>2 weeks) 3D cultures, thereby contributing to cell dysfunction. The results suggest that this 3D tissue engineered brain-like model may provide useful readouts related to PD neuro-toxicology research.

Published
2019
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25. A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability.

Author

Bonzanni M, DiFrancesco JC, Milanesi R, Campostrini G, Castellotti B, Bucchi A, Baruscotti M, Ferrarese C, Franceschetti S, Canafoglia L, Ragona F, Freri E, Labate A, Gambardella A, Costa C, Rivolta I, Gellera C, Granata T, Barbuti A, and DiFrancesco D

Subjects
Action Potentials physiology, Amino Acid Sequence, Animals, Animals, Newborn, CHO Cells, Cells, Cultured, Cricetinae, Cricetulus, Epilepsy, Generalized physiopathology, Female, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels chemistry, Male, Pedigree, Potassium Channels chemistry, Protein Structure, Secondary, Rats, Young Adult, Epilepsy, Generalized diagnosis, Epilepsy, Generalized genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels genetics, Mutation genetics, Neurons physiology, Potassium Channels genetics
Abstract

The causes of genetic epilepsies are unknown in the majority of patients. HCN ion channels have a widespread expression in neurons and increasing evidence demonstrates their functional involvement in human epilepsies. Among the four known isoforms, HCN1 is the most expressed in the neocortex and hippocampus and de novo HCN1 point mutations have been recently associated with early infantile epileptic encephalopathy. So far, HCN1 mutations have not been reported in patients with idiopathic epilepsy. Using a Next Generation Sequencing approach, we identified the de novo heterozygous p.Leu157Val (c.469C > G) novel mutation in HCN1 in an adult male patient affected by genetic generalized epilepsy (GGE), with normal cognitive development. Electrophysiological analysis in heterologous expression model (CHO cells) and in neurons revealed that L157V is a loss-of-function, dominant negative mutation causing reduced HCN1 contribution to net inward current and responsible for an increased neuronal firing rate and excitability, potentially predisposing to epilepsy. These data represent the first evidence that autosomal dominant missense mutations of HCN1 can also be involved in GGE, without the characteristics of epileptic encephalopathy reported previously. It will be important to include HCN1 screening in patients with GGE, in order to extend the knowledge of the genetic causes of idiopathic epilepsies, thus paving the way for the identification of innovative therapeutic strategies., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2018
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26. A Loss-of-Function HCN4 Mutation Associated With Familial Benign Myoclonic Epilepsy in Infancy Causes Increased Neuronal Excitability.

Author

Campostrini G, DiFrancesco JC, Castellotti B, Milanesi R, Gnecchi-Ruscone T, Bonzanni M, Bucchi A, Baruscotti M, Ferrarese C, Franceschetti S, Canafoglia L, Ragona F, Freri E, Labate A, Gambardella A, Costa C, Gellera C, Granata T, Barbuti A, and DiFrancesco D

Abstract

HCN channels are highly expressed and functionally relevant in neurons and increasing evidence demonstrates their involvement in the etiology of human epilepsies. Among HCN isoforms, HCN4 is important in cardiac tissue, where it underlies pacemaker activity. Despite being expressed also in deep structures of the brain, mutations of this channel functionally shown to be associated with epilepsy have not been reported yet. Using Next Generation Sequencing for the screening of patients with idiopathic epilepsy, we identified the p.Arg550Cys (c.1648C>T) heterozygous mutation on HCN4 in two brothers affected by benign myoclonic epilepsy of infancy. Functional characterization in heterologous expression system and in neurons showed that the mutation determines a loss of function of HCN4 contribution to activity and an increase of neuronal discharge, potentially predisposing to epilepsy. Expressed in cardiomyocytes, mutant channels activate at slightly more negative voltages than wild-type (WT), in accordance with borderline bradycardia. While HCN4 variants have been frequently associated with cardiac arrhythmias, these data represent the first experimental evidence that functional alteration of HCN4 can also be involved in human epilepsy through a loss-of-function effect and associated increased neuronal excitability. Since HCN4 appears to be highly expressed in deep brain structures only early during development, our data provide a potential explanation for a link between dysfunctional HCN4 and infantile epilepsy. These findings suggest that it may be useful to include HCN4 screening to extend the knowledge of the genetic causes of infantile epilepsies, potentially paving the way for the identification of innovative therapeutic strategies.

Published
2018
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27. The expression of the rare caveolin-3 variant T78M alters cardiac ion channels function and membrane excitability.

Author

Campostrini G, Bonzanni M, Lissoni A, Bazzini C, Milanesi R, Vezzoli E, Francolini M, Baruscotti M, Bucchi A, Rivolta I, Fantini M, Severi S, Cappato R, Crotti L, J Schwartz P, DiFrancesco D, and Barbuti A

Subjects
3T3 Cells, Animals, Arrhythmias, Cardiac genetics, Arrhythmias, Cardiac metabolism, Arrhythmias, Cardiac physiopathology, Caveolae metabolism, Caveolin 1 deficiency, Caveolin 1 genetics, Computer Simulation, Fibroblasts ultrastructure, Heart Rate, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels metabolism, Ion Channel Gating, Kinetics, Kv1.5 Potassium Channel genetics, Kv1.5 Potassium Channel metabolism, Mice, Mice, Knockout, Models, Cardiovascular, Muscle Proteins genetics, Muscle Proteins metabolism, Myocardial Contraction, Myocytes, Cardiac ultrastructure, Potassium Channels genetics, Potassium Channels metabolism, Rats, Sprague-Dawley, Transfection, Action Potentials, Caveolin 3 genetics, Caveolin 3 metabolism, Fibroblasts metabolism, Mutation, Myocytes, Cardiac metabolism
Abstract

Aims: Caveolinopathies are a family of genetic disorders arising from alterations of the caveolin-3 (cav-3) gene. The T78M cav-3 variant has been associated with both skeletal and cardiac muscle pathologies but its functional contribution, especially to cardiac diseases, is still controversial. Here, we evaluated the effect of the T78M cav-3 variant on cardiac ion channel function and membrane excitability., Methods and Results: We transfected either the wild type (WT) or T78M cav-3 in caveolin-1 knock-out mouse embryonic fibroblasts and found by immunofluorescence and electron microscopy that both are expressed at the plasma membrane and form caveolae. Two ion channels known to interact and co-immunoprecipitate with the cav-3, hKv1.5 and hHCN4, interact also with T78M cav-3 and reside in lipid rafts. Electrophysiological analysis showed that the T78M cav-3 causes hKv1.5 channels to activate and inactivate at more hyperpolarized potentials and the hHCN4 channels to activate at more depolarized potentials, in a dominant way. In spontaneously beating neonatal cardiomyocytes, the expression of the T78M cav-3 significantly increased action potential peak-to-peak variability without altering neither the mean rate nor the maximum diastolic potential. We also found that in a small cohort of patients with supraventricular arrhythmias, the T78M cav-3 variant is more frequent than in the general population. Finally, in silico analysis of both sinoatrial and atrial cell models confirmed that the T78M-dependent changes are compatible with a pro-arrhythmic effect., Conclusion: This study demonstrates that the T78M cav-3 induces complex modifications in ion channel function that ultimately alter membrane excitability. The presence of the T78M cav-3 can thus generate a susceptible substrate that, in concert with other structural alterations and/or genetic mutations, may become arrhythmogenic., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology)

Published
2017
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