Author:
Bouvet Marion,Claude Olivier,Roux Maguelonne,Skelly Dan,Masurkar Nihar,Mougenot Nathalie,Nadaud Sophie,Blanc Catherine,Delacroix Clément,Chardonnet Solenne,Pionneau Cédric,Perret Claire,Yaniz-Galende Elisa,Rosenthal Nadia,Trégouët David-Alexandre,Marazzi Giovanna,Silvestre Jean-Sébastien,Sassoon David,Hulot Jean-Sébastien
Abstract
AbstractThere is currently no therapy to limit the development of cardiac fibrosis and consequent heart failure. We have recently shown that cardiac fibrosis post-myocardial infarction (MI) can be regulated by resident cardiac cells with a fibrogenic signature and identified by the expression of PW1 (Peg3). Here we identify αV-integrin (CD51) as an essential regulator of cardiac PW1+ cells fibrogenic behavior. We used transcriptomic and proteomic approaches to identify specific cell-surface markers for cardiac PW1+ cells and found that αV-integrin (CD51) was expressed in almost all cardiac PW1+ cells (93% ± 1%), predominantly as the αVβ1 complex. αV-integrin is a subunit member of the integrin family of cell adhesion receptors and was found to activate complex of latent transforming growth factor beta (TGFβ at the surface of cardiac PW1+ cells. Pharmacological inhibition of αV-integrin reduced the profibrotic action of cardiac PW1+CD51+ cells and was associated with improved cardiac function and animal survival following MI coupled with a reduced infarct size and fibrotic lesion. These data identify a targetable pathway that regulates cardiac fibrosis in response to an ischemic injury and demonstrate that pharmacological inhibition of αV-integrin could reduce pathological outcomes following cardiac ischemia.
Funder
GENMED Laboratory of Excellence on Medical Genomics
Fondation Leducq
Agence Nationale de la Recherche
Era-CVD
Publisher
Springer Science and Business Media LLC
Cited by
34 articles.
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