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168 results on '"Cavalca, V."'

1. PB0124 Treatment with PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia Lowers Plasma Levels of Platelet Activating Factor and its Precursors: A Combined Metabolomic and Lipidomic Approach

Author

Calcaterra, I., primary, Di Minno, A., additional, Orsini, R., additional, Chiesa, M., additional, Cavalca, V., additional, Tripaldella, M., additional, Anesi, A., additional, Fiorelli, S., additional, Eligini, S., additional, Palermo, V., additional, Donnarumma, S., additional, Tufano, A., additional, Iannuzzo, G., additional, Colombo, G., additional, Tremoli, E., additional, Porro, B., additional, and Di Minno, M., additional

Published
2023
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2. Treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia lowers plasma levels of platelet activating factor and its precursors: A combined metabolomic and lipidomic approach

Author

Di Minno, A., primary, Calcaterra, I.L., additional, Orsini, R., additional, Chiesa, M., additional, Cavalca, V., additional, Anesi, A., additional, Fiorelli, S., additional, Eligini, S., additional, Colombo, G., additional, Donnarumma, S., additional, Palermo, V., additional, Tremoli, E., additional, Porro, B., additional, and Di Minno, M.N.D., additional

Published
2023
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3. Platelet and Endothelial Activation as Potential Mechanisms Behind the Thrombotic Complications of COVID-19 Patients

Author

Canzano, P, Brambilla, M, Porro, B, Cosentino, N, Tortorici, E, Vicini, S, Poggio, P, Cascella, A, Pengo, M, Veglia, F, Fiorelli, S, Bonomi, A, Cavalca, V, Trabattoni, D, Andreini, D, Omodeo Sale, E, Parati, G, Tremoli, E, Camera, M, Canzano P., Brambilla M., Porro B., Cosentino N., Tortorici E., Vicini S., Poggio P., Cascella A., Pengo M., Veglia F., Fiorelli S., Bonomi A., Cavalca V., Trabattoni D., Andreini D., Omodeo Sale E., Parati G., Tremoli E., Camera M., Canzano, P, Brambilla, M, Porro, B, Cosentino, N, Tortorici, E, Vicini, S, Poggio, P, Cascella, A, Pengo, M, Veglia, F, Fiorelli, S, Bonomi, A, Cavalca, V, Trabattoni, D, Andreini, D, Omodeo Sale, E, Parati, G, Tremoli, E, Camera, M, Canzano P., Brambilla M., Porro B., Cosentino N., Tortorici E., Vicini S., Poggio P., Cascella A., Pengo M., Veglia F., Fiorelli S., Bonomi A., Cavalca V., Trabattoni D., Andreini D., Omodeo Sale E., Parati G., Tremoli E., and Camera M.

Abstract

The authors hypothesized that the cytokine storm described in COVID-19 patients may lead to consistent cell-based tissue factor (TF)-mediated activation of coagulation, procoagulant microvesicles (MVs) release, and massive platelet activation. COVID-19 patients have higher levels of TF+ platelets, TF+ granulocytes, and TF+ MVs than healthy subjects and coronary artery disease patients. Plasma MV-associated thrombin generation is present in prophylactic anticoagulated patients. A sustained platelet activation in terms of P-selectin expression and platelet–leukocyte aggregate formation, and altered nitric oxide/prostacyclin synthesis are also observed. COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to that observed in vivo. This effect was blunted by pre-incubation with tocilizumab, aspirin, or a P2Y12 inhibitor.

Published
2021

6. Netrin-1 in atherosclerosis: Relationship between human macrophage intracellular levels and in vivo plaque morphology

Author

Fiorelli, S., Cosentino, N., Porro, B., Fabbiocchi, F., Niccoli, G., Fracassi, F., Capra, N., Barbieri, S., Crea, F., Marenzi, G., Cavalca, V., Tremoli, E., Eligini, S., Niccoli G. (ORCID:0000-0002-3187-6262), Fracassi F., Crea F. (ORCID:0000-0001-9404-8846), Fiorelli, S., Cosentino, N., Porro, B., Fabbiocchi, F., Niccoli, G., Fracassi, F., Capra, N., Barbieri, S., Crea, F., Marenzi, G., Cavalca, V., Tremoli, E., Eligini, S., Niccoli G. (ORCID:0000-0002-3187-6262), Fracassi F., and Crea F. (ORCID:0000-0001-9404-8846)

Abstract

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.

Published
2021

11. Obesity is associated with impaired responsiveness to once-daily low-dose aspirin and in vivo platelet activation

Author

Petrucci, G, Zaccardi, F, Giaretta, A, Cavalca, V, Capristo, E, Cardillo, C, Pitocco, D, Porro, B, Schinzari, F, Toffolo, G, Tremoli, E, Rocca, B, Petrucci G (ORCID:0000-0002-9280-3673), Capristo E (ORCID:0000-0002-5753-3495), Pitocco D (ORCID:0000-0002-6220-686X), Schinzari F, Tremoli E, Rocca B (ORCID:0000-0001-8304-6423), Petrucci, G, Zaccardi, F, Giaretta, A, Cavalca, V, Capristo, E, Cardillo, C, Pitocco, D, Porro, B, Schinzari, F, Toffolo, G, Tremoli, E, Rocca, B, Petrucci G (ORCID:0000-0002-9280-3673), Capristo E (ORCID:0000-0002-5753-3495), Pitocco D (ORCID:0000-0002-6220-686X), Schinzari F, Tremoli E, and Rocca B (ORCID:0000-0001-8304-6423)

Abstract

Background: The prevalence and degree of obesity is rising worldwide, increases cardiovascular risk, modifies body composition and organ function, and potentially affects the pharmacokinetics and/or pharmacodynamics of drugs. Objectives: To investigate the pharmacodynamics of once-daily low-dose aspirin in healthy obese subjects, and to assess whether body weight (BW) and body mass index (BMI) affect the pharmacology of aspirin. Patients/methods: Otherwise healthy, obese (BMI > 30 kg/m2 ) subjects were studied before and after 3-4 weeks of 100-mg once-daily aspirin intake. Aspirin pharmacodynamics were assessed according to serum thromboxane (TX) B2 levels measured at 4 hours, 24 hours (i.e., posologic interval) and 48 hours after the last witnessed intake; age-matched and sex-matched non-obese controls were included. A previously calibrated pharmacokinetic/pharmacodynamic in silico model of aspirin was used to fit serum TXB2 data from obese subjects. At baseline, the major urinary TXA2 and prostacyclin metabolites, urinary isoprostane and plasma inflammatory biomarkers were measured. Results: In 16 obese subjects (aged 47 ± 11 years; BMI of 39.4 ± 5.1 kg/m2 ), residual serum TXB2 values between 4 and 48 hours after aspirin intake were increased 3- to 5-fold as compared with controls. At 24 hours, the residual serum TXB2 level was log-linearly associated with body size over a wide range of BMI and BW values, without any apparent threshold. The in silico model predicted that reduced aspirin bioavailability would be inversely related to body size and rescued by 200 mg of aspirin once daily or 85 mg twice daily. Baseline urinary TXA2 metabolite, isoprostane and plasma C-reactive protein levels were significantly increased in obese subjects. Conclusions: Obesity is associated with impaired aspirin responsiveness, largely because of body size. Impaired inhibition of platelet activation by conventional low-dose aspirin may affect antithrombotic efficacy.

Published
2019

12. Obesity is associated with in vivo platelet activation and impaired responsiveness to once-daily, low-dose aspirin

Author

Petrucci, Giovanna, Zaccardi, F., Giaretta, A., Cavalca, V., Capristo, Esmeralda, Cardillo, Carmine, Pitocco, Dario, Porro, B., Schinzari, Francesca, Toffolo, G., Tremoli, E., Rocca, Bianca, Petrucci G. (ORCID:0000-0002-9280-3673), Capristo E. (ORCID:0000-0002-5753-3495), cardillo c. (ORCID:0000-0001-5182-3005), Pitocco D. (ORCID:0000-0002-6220-686X), Schinzari F., Rocca B. (ORCID:0000-0001-8304-6423), Petrucci, Giovanna, Zaccardi, F., Giaretta, A., Cavalca, V., Capristo, Esmeralda, Cardillo, Carmine, Pitocco, Dario, Porro, B., Schinzari, Francesca, Toffolo, G., Tremoli, E., Rocca, Bianca, Petrucci G. (ORCID:0000-0002-9280-3673), Capristo E. (ORCID:0000-0002-5753-3495), cardillo c. (ORCID:0000-0001-5182-3005), Pitocco D. (ORCID:0000-0002-6220-686X), Schinzari F., and Rocca B. (ORCID:0000-0001-8304-6423)

Abstract

Obesity is raising worldwide, increases cardiovascular risk, modifies body composition and organ function, and potentially affects drug's pharmacokinetics and/or pharmacodynamics. OBJECTIVES: To investigate pharmacodynamics of once-daily low-dose aspirin in healthy obese subjects and to assess whether body weight (BW) or body mass index (BMI) would affect aspirin pharmacology. PATIENTS/METHODS: Otherwise healthy, obese (BMI>30kg/m2 ) subjects were studied before and after 3-4 weeks of 100mg once-daily aspirin. Aspirin pharmacodynamics was assessed by serum thromboxane (TX)B2 measured at 4, 24 (i.e. posological interval) and 48 hours after the last witnessed intake; age- and sex-matched non-obese controls were included. A previously-calibrated pharmacokinetic/pharmacodynamic in silico model of aspirin was used to fit serum TXB2 data from obese subjects. At baseline the major urinary TXA2 and prostacyclin metabolites, urinary isoprostane and plasma inflammatory biomarkers were measured. RESULTS: In sixteen obese subjects (47±11 years, BMI 39.4±5.1 kg/m2 ), residual serum TXB2 values between 4 and 48 hours post-aspirin were 3 to 5 folds increased compared to controls. At 24 hours, residual serum TXB2 was log-linearly associated with body size over a wide range of BMI and BW values, without any apparent threshold. The in silico model predicted reduced aspirin bioavailability inversely related to body size and rescued by 200 mg once-daily or 85 mg twice-daily. Baseline urinary TXA2 metabolite, isoprostane and plasma C-reactive protein levels were significantly increased in obese subjects. CONCLUSIONS: Obesity is associated with impaired aspirin responsiveness, largely due to body size. Impaired inhibition of platelet activation by conventional low-dose aspirin may affect antithrombotic efficacy.

Published
2019

13. The Aspirin Regimens in Essential Thrombocythemia (ARES) phase II randomized trial design: Implementation of the serum thromboxane B(2) assay as an evaluation tool of different aspirin dosing regimens in the clinical setting

Author

De Stefano, Valerio, Rocca, Bianca, Tosetto, A, Soldati, Denise, Petrucci, Giovanna, Beggiato, E, Bertozzi, I, Betti, Silvia, Carli, G, Carpenedo, M, Cattaneo, D, Cavalca, V, Dragani, A, Elli, E, Finazzi, G, Iurlo, A, Lanzarone, G, Lissandrini, L, Palandri, F, Paoli, C, Rambaldi, A, Ranalli, Paola, Randi, Ml, Ricco, A, Rossi, Elena, Ruggeri, M, Specchia, G, Timillero, A, Turnu, L, Vianelli, N, Vannucchi, Am, Rodeghiero, F, Patrono, Carlo, De Stefano V (ORCID:0000-0002-5178-5827), Rocca B (ORCID:0000-0001-8304-6423), Soldati D, Petrucci G (ORCID:0000-0002-9280-3673), Betti S, Ranalli P, Rossi E (ORCID:0000-0002-7572-9379), Patrono C, De Stefano, Valerio, Rocca, Bianca, Tosetto, A, Soldati, Denise, Petrucci, Giovanna, Beggiato, E, Bertozzi, I, Betti, Silvia, Carli, G, Carpenedo, M, Cattaneo, D, Cavalca, V, Dragani, A, Elli, E, Finazzi, G, Iurlo, A, Lanzarone, G, Lissandrini, L, Palandri, F, Paoli, C, Rambaldi, A, Ranalli, Paola, Randi, Ml, Ricco, A, Rossi, Elena, Ruggeri, M, Specchia, G, Timillero, A, Turnu, L, Vianelli, N, Vannucchi, Am, Rodeghiero, F, Patrono, Carlo, De Stefano V (ORCID:0000-0002-5178-5827), Rocca B (ORCID:0000-0001-8304-6423), Soldati D, Petrucci G (ORCID:0000-0002-9280-3673), Betti S, Ranalli P, Rossi E (ORCID:0000-0002-7572-9379), and Patrono C

Abstract

Once-daily (od), low-dose aspirin (75–100 mg) is recommended to reduce the thrombotic risk of patients with essential thrombocytemia (ET). This practice is based on data extrapolated from other high-risk patients and an aspirin trial in polycythemia vera, with the assumption of similar aspirin pharmacodynamics in the two settings. However, the pharmacodynamics of low-dose aspirin is impaired in ET, reflecting accelerated renewal of platelet cyclooxygenase (COX)-1. ARES is a parallel-arm, placebo-controlled, randomized, dose-finding, phase II trial enrolling 300 ET patients to address two main questions. First, whether twice or three times 100 mg aspirin daily dosing is superior to the standard od regimen in inhibiting platelet thromboxane (TX)A2 production, without inhibiting vascular prostacyclin biosynthesis. Second, whether long-term persistence of superior biochemical efficacy can be safely maintained with multiple vs. single dosing aspirin regimen. Considering that the primary study end point is serum TXB2, a surrogate biomarker of clinical efficacy, a preliminary exercise of reproducibility and validation of this biomarker across all the 11 participating centers was implemented. The results of this preliminary phase demonstrate the importance of controlling reproducibility of biomarkers in multicenter trials and the feasibility of using serum TXB2 as a reliable end point for dose-finding studies of novel aspirin regimens.

Published
2018

17. On-pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens

Author

Cavalca, V., Rocca, Bianca, Veglia, F., Petrucci, Giovanna, Porro, B., Myasoedova, V., De Cristofaro, Raimondo, Turnu, L., Bonomi, A., Songia, P., Cavallotti, L., Zanobini, M., Camera, M., Alamanni, F., Parolari, A., Patrono, Carlo, Tremoli, E., Rocca, Bianca (ORCID:0000-0001-8304-6423), Petrucci, Giovanna (ORCID:0000-0002-9280-3673), De Cristofaro, Raimondo (ORCID:0000-0002-8066-8849), Cavalca, V., Rocca, Bianca, Veglia, F., Petrucci, Giovanna, Porro, B., Myasoedova, V., De Cristofaro, Raimondo, Turnu, L., Bonomi, A., Songia, P., Cavallotti, L., Zanobini, M., Camera, M., Alamanni, F., Parolari, A., Patrono, Carlo, Tremoli, E., Rocca, Bianca (ORCID:0000-0001-8304-6423), Petrucci, Giovanna (ORCID:0000-0002-9280-3673), and De Cristofaro, Raimondo (ORCID:0000-0002-8066-8849)

Abstract

On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100 mg once-daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once-daily, 100 mg twice-daily, or 200 mg once-daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once-daily showed a significant increase in serum thromboxane (TX)B2within the 24-hour dosing interval and urinary TXA2metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB2and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.

Published
2017

20. In vivo platelet activation and aspirin responsiveness in type 1 diabetes mellitus

Author

Zaccardi, Francesco, Rizzi, Alessandro, Petrucci, Giovanna, Ciaffardini, F, Tanese, Luigi, Pagliaccia, Francesca, Cavalca, V, Ciminello, Angela Maria, Habib, A, Squellerio, I, Rizzo, P, Tremoli, E, Rocca, Bianca, Pitocco, Dario, and Patrono, Carlo

Subjects
platelet, diabetes, Settore BIO/14 - FARMACOLOGIA, Settore MED/09 - MEDICINA INTERNA, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Settore MED/13 - ENDOCRINOLOGIA
Published
2015

21. Neurohormonal activation is associated with increased levels of plasma matrix metalloproteinase-2 in human heart failure

Author

Banfi, C, Cavalca, V, Veglia, F, Brioschi, M, Barcella, S, Mussoni, L, Boccotti, L, Tremoli, E, Biglioli, P, Agostoni, P, Banfi C., Cavalca V., Veglia F., Brioschi M., Barcella S., Mussoni L., Boccotti L., Tremoli E., Biglioli P., Agostoni P., Banfi, C, Cavalca, V, Veglia, F, Brioschi, M, Barcella, S, Mussoni, L, Boccotti, L, Tremoli, E, Biglioli, P, Agostoni, P, Banfi C., Cavalca V., Veglia F., Brioschi M., Barcella S., Mussoni L., Boccotti L., Tremoli E., Biglioli P., and Agostoni P.

Abstract

Aims: Development of heart failure depends on systemic and molecular abnormalities among which are the activation of neurohormonal systems and the increase of matrix metalloproteinases (MMPs). This study assessed the relationship between catecholamines and active MMPs in vivo in patients with severe congestive heart failure (CHF) and in vitro in human cardiac fibroblasts. Methods and results: Forty patients with CHF due to dilated cardiomyopathy, either idiopathic (n = 20) or secondary to ischaemic heart disease (n = 20), were compared with 20 healthy subjects. Plasma MMP-2 and MMP-9 activity, but not TIMP-2, were significantly higher in patients than in controls (median MMP-2, 270 vs. 214 ng/mL, P = 0.006; MMP-9 16.3 vs. 8.7 ng/mL, P < 0.0001). Similarly, noradrenaline, but not adrenaline, was significantly higher in patients (noradrenaline 645 vs. 157 pg/mL, P < 0.0001; adrenaline 86.0 vs. 72.6 pg/mL, P = 0.68). No difference in any parameter was observed between patient groups. The intra-group correlation between MPP-2 and noradrenaline was significant (r = 0.33, P = 0.01); indeed, noradrenaline appear to be a predictor of MMP-2. Moreover, this catecholamine increased MMP-2 in human cardiac fibroblasts. Conclusions: The positive correlation between noradrenaline and MMP-2 in severe CHF patients, together with the in vitro induction of MMP-2 by this catecholamine, suggests a potential biochemical link between noradrenaline and MMP-2.

Published
2005

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

Author

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

Published
2016
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24. In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythemia

Author

Cavalca, V, Rocca, Bianca, Squellerio, I, Dragani, A, Barbieri, S, Veglia, F, Pagliaccia, Francesca, Porro, B, Tremoli, E, Patrono, Carlo, Rocca, Bianca (ORCID:0000-0001-8304-6423), Cavalca, V, Rocca, Bianca, Squellerio, I, Dragani, A, Barbieri, S, Veglia, F, Pagliaccia, Francesca, Porro, B, Tremoli, E, Patrono, Carlo, and Rocca, Bianca (ORCID:0000-0001-8304-6423)

Abstract

Essential Thrombocythemia (ET) is characterized by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterized in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1 (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomized to different 7-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hrs after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials.

Published
2014

26. Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: Patterns and differences

Author

Cavalca, V, Tremoli, E, Porro, B, Veglia, F, Myasoedova, V, Squellerio, I, Manzone, D, Zanobini, M, Trezzi, M, Di Minno, M, Werba, J, Tedesco, C, Alamanni, F, Parolari, A, Parolari, A., MANZONE, DANIELA MADDALENA, Cavalca, V, Tremoli, E, Porro, B, Veglia, F, Myasoedova, V, Squellerio, I, Manzone, D, Zanobini, M, Trezzi, M, Di Minno, M, Werba, J, Tedesco, C, Alamanni, F, Parolari, A, Parolari, A., and MANZONE, DANIELA MADDALENA

Abstract

OBJECTIVES: We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS: In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS: Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS: Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve reg

Published
2013

39. Anesthetic propofol enhances plasma gamma-tocopherol levels in patients undergoing cardiac surgery.

Author

Cavalca V, Colli S, Veglia F, Eligini S, Zingaro L, Squellerio I, Rondello N, Cighetti G, Tremoli E, and Sisillo E

Abstract

BACKGROUND: Propofol (2,6-diisopropylphenol) is an anesthetic drug with antioxidant and antiinflammatory properties, documented both in vitro and in experimental models of ischemia-reperfusion injury and septic shock. These properties have been related to the similarity of its chemical structure to that of endogenous tocopherols, which are phenol-containing radical scavengers. This study evaluated the effects of propofol on alpha- and gamma-tocopherol (alpha- and gamma-T) levels and on selected markers of oxidant-antioxidant and inflammatory status in patients undergoing cardiac surgery. METHODS: Patients were randomly assigned for anesthesia with either propofol (propofol group, n = 22) or sevoflurane (control group, n = 21). Plasma levels of alpha- and gamma-T, individual antioxidant capacity, malondialdehyde, and interleukin 10 were measured before, during, and after anesthesia. In addition, levels of the proinflammatory prostaglandin E2 as a marker of cyclooxygenase-2 activity and those of interleukin 10 were measured in whole blood cultured with bacterial lipopolysaccharide. RESULTS: Gamma-T levels increased significantly during surgery in propofol group (P < 0.0001 vs. control group). By contrast, alpha-T similarly decreased in both groups. Malondialdehyde and interleukin 10 increased markedly and individual antioxidant capacity decreased, without differences between groups. Prostaglandin E2 levels measured 24 h after anesthesia induction were significantly lower in the propofol than in the control group. In vitro studies highlighted the different capacity of gamma- and alpha-T to impair prostaglandin E2 synthesis by human monocytes challenged with bacterial lipopolysaccharide. CONCLUSIONS: The antiinflammatory properties of propofol that may be linked to its effect on gamma-T levels could be relevant in controlling the inflammatory response that accompanies tissue injury during reperfusion. [ABSTRACT FROM AUTHOR]

Published
2008
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43. P703 NO synthetic pathway and oxidative stress in microvascular angina: assessment in red blood cells and plasma.

Author

Porro, B, Eligini, S, Veglia, F, Lualdi, A, Squellerio, I, Fiorelli, S, Werba, JP, Tremoli, E, and Cavalca, V

Subjects
NITRIC-oxide synthases, OXIDATIVE stress, MICROVASCULAR angina, ERYTHROCYTES, BLOOD plasma, ARGININE
Abstract

A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. Recent studies have shown that red blood cells (RBCs) participate in NO formation in the bloodstream. The aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). We determined substrate, products (Arg, L-citrulline and L-ornithine) and inhibitors (asymmetric- and symmetric dimethylarginine and monomethylarginine) of NO synthesis in parallel to reduced and oxidized form of glutathione. MVA patients show alterations in the ability of RBCs to produce NO, based on an increase of NO synthesis inhibitors parallel to that found in plasma and a reduction of NO synthase expression. When summary scores of NO synthesis and oxidative stress were computed, both patient groups were associated with a positive score and a negative NO score. This finding points out to an impairement of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis. [ABSTRACT FROM PUBLISHER]

Published
2014
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44. Platelet and Endothelial Activation as Potential Mechanisms Behind the Thrombotic Complications of COVID-19 Patients

Author

Daniele Andreini, Fabrizio Veglia, Marta Brambilla, Alice Bonomi, Benedetta Porro, Martino F. Pengo, Viviana Cavalca, Stefano Vicini, Marina Camera, Paola Canzano, Daniela Trabattoni, Andrea Cascella, Paolo Poggio, Elena Tortorici, Emanuela Omodeo Salè, Susanna Fiorelli, Gianfranco Parati, Elena Tremoli, Nicola Cosentino, Canzano, P, Brambilla, M, Porro, B, Cosentino, N, Tortorici, E, Vicini, S, Poggio, P, Cascella, A, Pengo, M, Veglia, F, Fiorelli, S, Bonomi, A, Cavalca, V, Trabattoni, D, Andreini, D, Omodeo Sale, E, Parati, G, Tremoli, E, and Camera, M

Subjects
0301 basic medicine, endothelium, 030204 cardiovascular system & hematology, Pharmacology, Nitric oxide, Endothelial activation, 03 medical and health sciences, chemistry.chemical_compound, Tissue factor, 0302 clinical medicine, P2Y12, platelet activation, Medicine, antiplatelet drug, Platelet, Platelet activation, Interleukin 6, IL-6, biology, business.industry, COVID-19, tissue factor, 030104 developmental biology, Coagulation, chemistry, inflammation, platelets, circulating microvesicle, biology.protein, Cardiology and Cardiovascular Medicine, business, Editorial Comment
Abstract

The authors hypothesized that the cytokine storm described in COVID-19 patients may lead to consistent cell-based tissue factor (TF)-mediated activation of coagulation, procoagulant microvesicles (MVs) release, and massive platelet activation. COVID-19 patients have higher levels of TF+ platelets, TF+ granulocytes, and TF+ MVs than healthy subjects and coronary artery disease patients. Plasma MV-associated thrombin generation is present in prophylactic anticoagulated patients. A sustained platelet activation in terms of P-selectin expression and platelet–leukocyte aggregate formation, and altered nitric oxide/prostacyclin synthesis are also observed. COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to that observed in vivo. This effect was blunted by pre-incubation with tocilizumab, aspirin, or a P2Y12 inhibitor.

Published
2021

45. An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab

Author

Andrea Anesi, Alessandro Di Minno, Ilenia Calcaterra, Viviana Cavalca, Maria Tripaldella, Benedetta Porro, Matteo Nicola Dario Di Minno, Anesi, A., Di Minno, A., Calcaterra, I., Cavalca, V., Tripaldella, M., Porro, B., and Di Minno, M. N. D.

Subjects
carbohydrates (lipids), Settore CHIM/01 - CHIMICA ANALITICA, PCSK-9, untargeted lipidomics, familial hypercholesterolemia, QH301-705.5, Medicine (miscellaneous), lipids (amino acids, peptides, and proteins), Biology (General), General Biochemistry, Genetics and Molecular Biology, Article
Abstract

Rationale: Familial hypercholesterolemia (FH) is caused by mutations in genes involved in low-density lipoprotein cholesterol (LDL-C) metabolism, including those for pro-protein convertase subtilisin/kexin type 9 (PCSK-9). The effect of PCSK-9 inhibition on the plasma lipidome has been poorly explored. Objective: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, the plasma lipidome of FH subjects before and at different time intervals during treatment with the PCSK-9 inhibitor Evolocumab was explored. Methods and Results: In 25 FH subjects, heterozygotes or compound heterozygotes for different LDL receptor mutations, untargeted lipidomic revealed significant reductions in 26 lipid classes belonging to phosphatidylcholine (PC), sphingomyelin (SM), ceramide (CER), cholesteryl ester (CE), triacylglycerol (TG) and phosphatidylinositol (PI). Lipid changes were graded between baseline and 4- and 12-week treatment. At 12-week treatment, five polyunsaturated diacyl PC, accounting for 38.6 to 49.2% of total PC at baseline; two ether/vinyl ether forms; seven SM; five CER and glucosyl/galactosyl-ceramide (HEX-CER) were reduced, as was the unsaturation index of HEX-CER and lactosyl—CER (LAC-CER). Although non quantitative modifications were observed in phosphatidylethanolamine (PE) during treatment with Evolocumab, shorter and more saturated fatty acyl chains were documented. Conclusions: Depletion of several phospholipid classes occurs in plasma of FH patients during treatment with the PCSK-9 inhibitor Evolocumab. The mechanism underlying these changes likely involves the de novo synthesis of SM and CER through the activation of the key enzyme sphingomyelin synthase by oxidized LDL and argues for a multifaceted system leading to vascular improvement in users of PCSK-9 inhibitors.

Published
2021

46. Treatment with PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia Lowers Plasma Levels of Platelet-Activating Factor and Its Precursors: A Combined Metabolomic and Lipidomic Approach

Author

Matteo Nicola Dario Di Minno, Benedetta Porro, Andrea Anesi, Sonia Eligini, Gualtiero I. Colombo, Viviana Cavalca, M. Tripaldella, Mattia Chiesa, Ilenia Calcaterra, Roberta Clara Orsini, Susanna Fiorelli, Alessandro Di Minno, Elena Tremoli, Di Minno, A., Orsini, R. C., Chiesa, M., Cavalca, V., Calcaterra, I., Tripaldella, M., Anesi, A., Fiorelli, S., Eligini, S., Colombo, G. I., Tremoli, E., Porro, B., and Di Minno, M. N. D.

Subjects
medicine.medical_specialty, Settore CHIM/01 - CHIMICA ANALITICA, Apolipoprotein B, QH301-705.5, Medicine (miscellaneous), Familial hypercholesterolemia, Creatine, General Biochemistry, Genetics and Molecular Biology, Article, PCSK9, chemistry.chemical_compound, Internal medicine, Medicine, Choline, Platelet activation, Biology (General), biology, familial hypercholesterolemia, business.industry, medicine.disease, untargeted metabolomics, Endocrinology, chemistry, LDL receptor, biology.protein, Kexin, lipids (amino acids, peptides, and proteins), business
Abstract

Introduction: Familial hypercholesterolemia (FH) is characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C) and is caused by mutations of genes involved in LDL-C metabolism, including LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Accordingly, PCSK9 inhibitors (PCSK9i) are effective in LDL-C reduction. However, no data are available on the pleiotropic effect of PCSK9i. To this end, we performed an untargeted metabolomics approach to gather a global view on changes in metabolic pathways in patients receiving treatment with PCSK9i. Methods: Twenty-five FH patients starting treatment with PCSK-9i were evaluated by an untargeted metabolomics approach at baseline (before PCSK9i treatment) and after 12 weeks of treatment. Results: All the 25 FH subjects enrolled were on maximal tolerated lipid-lowering therapy prior to study entry. After a 12 week treatment with PCSK9i, we observed an expected significant reduction in LDL-cholesterol levels (from 201.0 ± 69.5 mg/dL to 103.0 ± 58.0 mg/dL, p &lt, 0.001). The LDL-C target was achieved in 36% of patients. After peak validation and correction, after 12 weeks of PCSK9i treatment as compared to baseline, we observed increments in creatine (p-value = 0.041), indole (p-value = 0.045), and indoleacrylic acid (p-value= 0.045) concentrations. Conversely, significant decreases in choline (p-value = 0.045) and phosphatidylcholine (p-value &lt, 0.01) together with a reduction in platelet activating factor (p-value = 0.041) were observed. Conclusions: Taking advantage of untargeted metabolomics, we first provided evidence of concomitant reductions in inflammation and platelet activation metabolites in FH patients receiving a 12 week treatment with PCSK9i.

Published
2021

47. Plasma phospholipid dysregulation in patients with cystathionine-β synthase deficiency

Author

Mattia Chiesa, Filomena Capasso, Filomena Morisco, Susanna Fiorelli, Elena Tremoli, Matteo Nicola Dario Di Minno, Andrea Anesi, Viviana Cavalca, Gualtiero I. Colombo, Benedetta Porro, Roberta Clara Orsini, Sonia Eligini, Alessandro Di Minno, F. Cirillo, Di Minno, A., Anesi, A., Chiesa, M., Cirillo, F., Colombo, G. I., Orsini, R. C., Capasso, F., Morisco, F., Fiorelli, S., Eligini, S., Cavalca, V., Tremoli, E., Porro, B., and Di Minno, M. N. D.

Subjects
Adult, Male, medicine.medical_specialty, Settore CHIM/01 - CHIMICA ANALITICA, Spectrometry, Mass, Electrospray Ionization, Homocysteine, Endocrinology, Diabetes and Metabolism, S-adenosylhomocysteine, Medicine (miscellaneous), 030209 endocrinology & metabolism, Homocystinuria, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Plasma untargeted lipidomics, Internal medicine, Lipidomics, medicine, Humans, Plasma untargeted lipidomic, Phosphatidylethanolamine-N-methyltransferase, Chromatography, High Pressure Liquid, Phospholipids, Aged, Dyslipidemias, chemistry.chemical_classification, Nutrition and Dietetics, S-adenosylmethionine, biology, Chemistry, Lysophosphatidylethanolamine, Lipidome, Middle Aged, medicine.disease, Cystathionine beta synthase, Endocrinology, Phosphatidylethanolamine N-methyltransferase, Case-Control Studies, biology.protein, lipids (amino acids, peptides, and proteins), Female, Cardiology and Cardiovascular Medicine, Biomarkers, Polyunsaturated fatty acid
Abstract

Background & aims: Patients with cystathionine β-synthase deficiency (CBSD) exhibit high circulating levels of homocysteine and enhanced lipid peroxidation. We have characterized the plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels. Methods and results: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, plasma lipids were determined with an untargeted lipidomics approach in 11 CBSD patients and 11 matched healthy subjects (CTRL). Compared to CTRL, CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p < 0.02), and depletion of phosphatidylcholine (PC; p = 0.02) and of lysophosphatidylcholine (LPC; p = 0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p = 0.015) and 5.3-fold (p = 0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r = 0.520; p = 0.019) was found. Conclusions: A novel biochemical abnormality in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE species is revealed by this lipidomic approach. Changes in plasma SAM and SAH concentrations are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, depletion of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with homocystinuria.

Published
2020

48. Relationship Between Plasma Osteopontin and Arginine Pathway Metabolites in Patients With Overt Coronary Artery Disease

Author

Donato Moschetta, Matteo Nicola Dario Di Minno, Benedetta Porro, Gianluca L. Perrucci, Vincenza Valerio, Valentina Alfieri, Ilaria Massaiu, Alexander N. Orekhov, Alessandro Di Minno, Paola Songia, Viviana Cavalca, Veronika A. Myasoedova, Paolo Poggio, Moschetta, D., Di Minno, M. N. D., Porro, B., Perrucci, G. L., Valerio, V., Alfieri, V., Massaiu, I., Orekhov, A. N., Di Minno, A., Songia, P., Cavalca, V., Myasoedova, V. A., and Poggio, P.

Subjects
0301 basic medicine, OPN, medicine.medical_specialty, Arginine, Physiology, 030204 cardiovascular system & hematology, medicine.disease_cause, lcsh:Physiology, endothelial dysfunction, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, atherosclerosi, stomatognathic system, Enos, nitric oxide, Physiology (medical), Internal medicine, medicine, Citrulline, Osteopontin, Endothelial dysfunction, lcsh:QP1-981, biology, business.industry, Ornithine, Brief Research Report, medicine.disease, biology.organism_classification, Arginase, 030104 developmental biology, Endocrinology, chemistry, citrulline, biology.protein, atherosclerosis, business, Oxidative stress
Abstract

Introduction Osteopontin (OPN) is involved in ectopic calcification. Its circulating form is upregulated in coronary artery disease (CAD) patients. Circulating OPN levels positively correlate with oxidative stress, one of the major triggers of endothelial dysfunction. Endothelial dysfunction is, in turn, associated with reduced nitric oxide (NO) bioavailability due to the impaired arginine pathway. The aim of this study was to better understand the correlations between OPN, oxidative stress markers, and the arginine pathway metabolites. Methods and results ELISA and mass spectrometry techniques have been used to evaluate circulating OPN and arginine pathway/oxidative stress metabolites, respectively, in twenty-five control subjects and thirty-three patients with overt atherosclerosis. OPN positively correlates with 2,3-dinor-8isoPGF2a levels (p = 0.02), ornithine (p = 0.01), ADMA (p = 0.001), SDMA (p = 0.03), and citrulline (p = 0.008) levels only in CAD patients. In addition, citrulline positively correlated with ADMA (p = 0.02) levels, possibly as result of other sources of citrulline biosynthetic pathways. Conclusion The association between OPN and impaired arginine/NO pathway could play a role in the inhibition of endothelial NO synthase (eNOS) and/or in the arginase activation in the context of CAD patients. However, further studies are needed to verify the cause-effect relationship between OPN, oxidative stress, and arginine/NO pathway dysregulation.

Published
2019

49. 8-Hydroxy-2-deoxyguanosine levels and heart failure: A systematic review and meta-analysis of the literature

Author

M. N. D. Di Minno, A. Di Minno, Benedetta Porro, Viviana Cavalca, Elena Tremoli, Linda Turnu, Isabella Squellerio, Di Minno, A, Turnu, L, Porro, B, Squellerio, I, Cavalca, V, Tremoli, E, and DI MINNO, Matteo

Subjects
0301 basic medicine, medicine.medical_specialty, Pathology, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030204 cardiovascular system & hematology, Gastroenterology, Severity of Illness Index, Ventricular Function, Left, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, Severity of illness, medicine, Humans, Meta-analysi, Prospective cohort study, Heart Failure, Creatinine, Nutrition and Dietetics, Chi-Square Distribution, business.industry, Myocardium, Deoxyguanosine, Stroke Volume, medicine.disease, Prognosis, Confidence interval, Up-Regulation, Oxidative Stress, 030104 developmental biology, chemistry, 8-Hydroxy-2'-Deoxyguanosine, Meta-analysis, Heart failure, Biomarker (medicine), Cardiology and Cardiovascular Medicine, business, Chi-squared distribution, Biomarkers, 8-OHdG, DNA Damage
Abstract

Background and aims The generation of reactive oxygen species (ROS) plays an important role in the etiology of several pathological conditions. High levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of oxidative damage of DNA, have been found in patients with heart failure (HF). We performed a meta-analysis of the literature to investigate the association between 8-OHdG levels and HF. Methods and results A systematic search was performed in the PubMed, Web of Science, Scopus, EMBASE databases and studies evaluating 8-OHdG levels in HF patients and controls were included. Differences between cases and controls were expressed as standard mean difference (SMD) or mean difference (MD) with pertinent 95% confidence intervals (95%CI). Impact of clinical and demographic features on effect size was assessed by meta-regression. Six studies (446 HF patients and 140 controls) were included in the analysis. We found that HF patients showed higher 8-OHdG levels than controls (SMD:0.89, 95%CI: 0.68, 1.10). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD:6.28 ng/mg creatinine, 95%CI: 4.01, 8.56) and in blood samples (MD:0.36 ng/ml, 95%CI: 0.04, 0.69). Interestingly, 8-OHdG levels progressively increased for increasing New York Heart Association (NYHA) class. Meta-regression models showed that none of clinical and demographic variables impacted on the difference in 8-OHdG levels among HF patients and controls. Conclusions 8-OHdG levels are higher in HF patients HF than in controls, with a progressive increase for increasing NYHA class. However, larger prospective studies are needed to test 8-OHdG as a biomarker of HF severity and progression.

Published
2016

50. Neurohormonal activation is associated with increased levels of plasma matrix metalloproteinase-2 in human heart failure

Author

Paolo Biglioli, Piergiuseppe Agostoni, Cristina Banfi, Elena Tremoli, Maura Brioschi, Luciana Mussoni, Fabrizio Veglia, Viviana Cavalca, Simona Barcella, Loredana Boccotti, Banfi, C, Cavalca, V, Veglia, F, Brioschi, M, Barcella, S, Mussoni, L, Boccotti, L, Tremoli, E, Biglioli, P, and Agostoni, P

Subjects
Cardiomyopathy, Dilated, Male, medicine.medical_specialty, Epinephrine, Heart disease, Immunoblotting, Cardiomyopathy, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Matrix metalloproteinase, Norepinephrine, In vivo, Internal medicine, Blood plasma, medicine, Humans, Myocytes, Cardiac, Metalloproteinase, Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica, Heart Failure, Neurotransmitter Agents, Tissue Inhibitor of Metalloproteinase-2, business.industry, Settore MED/23 - Chirurgia Cardiaca, Dilated cardiomyopathy, Fibroblasts, Middle Aged, Prognosis, medicine.disease, Endocrinology, Heart failure, Catecholamine, Noradrenaline, Settore BIO/14 - Farmacologia, Matrix Metalloproteinase 2, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Aims: Development of heart failure depends on systemic and molecular abnormalities among which are the activation of neurohormonal systems and the increase of matrix metalloproteinases (MMPs). This study assessed the relationship between catecholamines and active MMPs in vivo in patients with severe congestive heart failure (CHF) and in vitro in human cardiac fibroblasts. Methods and results: Forty patients with CHF due to dilated cardiomyopathy, either idiopathic (n = 20) or secondary to ischaemic heart disease (n = 20), were compared with 20 healthy subjects. Plasma MMP-2 and MMP-9 activity, but not TIMP-2, were significantly higher in patients than in controls (median MMP-2, 270 vs. 214 ng/mL, P = 0.006; MMP-9 16.3 vs. 8.7 ng/mL, P < 0.0001). Similarly, noradrenaline, but not adrenaline, was significantly higher in patients (noradrenaline 645 vs. 157 pg/mL, P < 0.0001; adrenaline 86.0 vs. 72.6 pg/mL, P = 0.68). No difference in any parameter was observed between patient groups. The intra-group correlation between MPP-2 and noradrenaline was significant (r = 0.33, P = 0.01); indeed, noradrenaline appear to be a predictor of MMP-2. Moreover, this catecholamine increased MMP-2 in human cardiac fibroblasts. Conclusions: The positive correlation between noradrenaline and MMP-2 in severe CHF patients, together with the in vitro induction of MMP-2 by this catecholamine, suggests a potential biochemical link between noradrenaline and MMP-2.

Published
2004

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