Bouleti C.,The Interdisciplinary Center |
Bouleti C.,French National Center for Scientific Research |
Bouleti C.,French Institute of Health and Medical Research |
Bouleti C.,University Paris Diderot |
And 22 more authors.
International Journal of Cardiology | Year: 2015
Background: No-reflow in ST-segment elevation acute myocardial infarction (STEMI) is associated with a poor clinical prognosis. Its pathophysiological mechanisms are not fully elucidated yet but enhanced vascular permeability plays a key role in this phenomenon. Angiopoietin-like 4 (ANGPTL4) has been implicated in vascular permeability in experimental models of acute myocardial infarction (AMI). We therefore sought to investigate whether baseline ANGPTL4 serum levels are associated with no-reflow after primary percutaneous coronary intervention (PPCI). Methods: We studied a group of 41 patients presenting with a first STEMI within 12 h of onset of symptoms and who underwent successful PPCI. Blood samples were obtained from all patients on admission before the start of the procedure, for ANGPTL4 level measurement. No-reflow was assessed by cardiac magnetic resonance imaging (MRI), the reference method. Results: MRI-detected no-reflow was observed in 20 patients (48.8%). Variables independently associated with no-reflow on multivariate logistic regression analysis were: lower ANGPTL4 serum levels (odds ratio 0.82, 95% CI 0.70-0.98, P = 0.02), higher troponin T peak (odds ratio 1.03, 95% CI 1.00-1.05, P = 0.03), higher incidence of left anterior descending coronary artery (LAD) as culprit artery (odds ratio 14.61, 95% CI 1.24- 172.49, P = 0.03), and higher C-reactive protein levels (odds ratio 1.18, 95% CI 1.00-1.39, P = 0.05). Conclusion: ANGPTL4 serum levels predict MRI-detected no-reflow after successful PPCI in STEMI patients. Given the recently demonstrated therapeutic role of ANGPTL4 in diminishing no-reflow and limiting infarct size in preclinical animal models, these findings in humans may open up new possibilities in the field of research. © 2015 Elsevier Ireland Ltd. All rights reserved. Source
Vite A.,University Pierre and Marie Curie |
Vite A.,French Institute of Health and Medical Research |
Gandjbakhch E.,University Pierre and Marie Curie |
Gandjbakhch E.,French Institute of Health and Medical Research |
And 22 more authors.
PLoS ONE | Year: 2013
Aims:Arrhythmogenic right ventricular Dysplasia/cardiomyopathy (ARVD/C) is an autosomal dominant inherited cardiomyopathy associated with ventricular arrhythmia, heart failure and sudden death. Genetic studies have demonstrated the central role of desmosomal proteins in this disease, where 50% of patients harbor a mutation in a desmosmal gene. However, clinical diagnosis of the disease remains difficult and molecular mechanisms appears heterogeneous and poorly understood. The aim of this study was to characterize the expression profile of desmosomal proteins in explanted ARVD/C heart samples, in order to identify common features of the disease.Methods and Results:We examined plakophilin-2, desmoglein-2, desmocollin-2, plakoglobin and β-catenin protein expression levels from seven independent ARVD/C heart samples compared to two ischemic, five dilated cardiomyopathy and one healthy heart sample as controls. Ventricular and septum sections were examined by immunoblot analysis of total heart protein extracts and by immunostaining.Immunoblots indicated significant decreases in desmoglein-2 and desmocollin-2, independent of any known underlying mutations, whereas immune-histochemical analysis showed normal localization of all desmosomal proteins. Quantitative RT-PCR revealed normal DSG2 and DSC2 mRNA transcript levels, suggesting increased protein turn-over rather than transcriptional down regulation.Conclusion:Reduced cardiac desmoglein-2 and desmocollin-2 levels appear to be specifically associated with ARVD/C, independent of underlying mutations. These findings highlight a key role of desmosomal cadherins in the pathophysiology of ARVD/C. Whether these reductions could be considered as specific markers for ARVD/C requires replication analysis. © 2013 Vite et al. Source