Search for molecular determinants of cardiovascular diseasesInstitut Pasteur de Lille
Inserm UMR 1167, Institut Pasteur de Lille, Université de Lille
1 rue du professeur Calmette
59019 Lille cedex, France - Lille
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The objectives of the team are to find biomarkers for diagnosis of heart failure by a translational approach from bench to bedside as summarized.
The research program of our team is dedicated to diseases related to aging, mainly cardiovascular diseases, which constitute major health issues in aging populations and constitute the world’s leading primary cause of death. The overall goal of our work is to identify new molecular determinants of heart failure (based on differential omics approaches developed in targeted clinical studies) in order to improve our knowledge of the underlying disease mechanisms by developing molecular and cellular explorations of these determinants in various animal and cell-based models. Our project was focused on omics targets identified to be involved on cardiac remodeling and validated for evidence of autophagy processes in cardiac cells: hyperphosphorylated desmin. Using an experimental rat model of heart failure, we identified that increased phosphorylation of desmin in heart promote depolymerization of desmin filaments that induce aggregates, toxic for the cardiomyocyte, contributing to cardiac remodeling and contractile dysfunction. We analyzed the three main proteolytic mechanisms (UPS, macroautophagy and chaperone-mediated autophagy [CMA]) that could be involved in phosphorylated desmin clearance. CMA was identified to be the main activated autophagy process and we speculate that CMA induction in cardiomyocyte might help to fight against formation of desmin aggregates in order to maintain cardiomyocyte survival.
– Dubois E, Richard V, Mulder P, Lamblin N, Drobecq H, Henry JP, Amouyel P, Bauters C, Pinet F. (2011) Decreased Serine207-phosphorylated troponin T as a biomarker for left ventricular remodeling after myocardial infarction. Eur. Heart J. 32:115-1213.
– Boytard L, Spear R, Chinetti-Gbaguidi G, Acosta-Martin AE, Vanhoutte J, Staels B, Lamblin N, Amouyel P, Haulon S, Pinet F. (2013) Role of proinflammatory CD68+MR- macrophages in peroxiredoxin-1 expression and in abdominal aortic aneurysms in humans. Arterioscler. Thromb. Vasc. Biol. 33:431-8.
– Kumarswamy R*, Bauters C*, Volkmann I, Maury F, Fetisch J, Holzmann A, Lemesle G, de Groote P, Pinet F, Thum T. (2014) The circulating long non-coding LIPCAR predicts survival in heart failure patients. Circ Res 114:1569-75.
– Lemesle G, Maury F, Beseme O, Ovart L, Amouyel P, Lamblin N, de Groote P, Bauters C, Pinet F. (2015) Multi-marker proteomic profiling for the prediction of cardiovascular mortality in patients with chronic heart failure. PlOs One;10:e0119265.
– Bouvet M, Dubois-Deruy E, Alayi TD, Mulder P, El Amranii M, Beseme O, Amouyel P, Richard R, Tomavo S, Pinet F. (2016). Increased levels of phosphorylated desmin and its degradation products in heart failure. Biochem Biophys Reports 6:54-62.
– Gupta SK, Foinquinos A, Thum S, Remke J, Zimmer K, Bauters C, de Groote P, Boon R, de Windt L, Preissl S, Hein L, Batkai S, Pinet F, Thum T. (2016) Preclinical development of a microRNA-based therapy for the infarcted heart of elderly individuals. J Am Coll Cardiol (sous presse).