Marion Bouvet, Olivier Claude, Maguelonne Roux, Dan Skelly, Nihar Masurkar, Nathalie Mougenot, Sophie Nadaud, Catherine Blanc, Clément Delacroix, Solenne Chardonnet, Cédric Pionneau, Claire Perret, Elisa Yaniz-Galende, Nadia Rosenthal, David-Alexandre Trégouët, Giovanna Marazzi, Jean-Sébastien Silvestre, David Sassoon, Jean-Sébastien Hulot
Scientific reports 2020 Jul 09There 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.)
Marion Bouvet, Olivier Claude, Maguelonne Roux, Dan Skelly, Nihar Masurkar, Nathalie Mougenot, Sophie Nadaud, Catherine Blanc, Clément Delacroix, Solenne Chardonnet, Cédric Pionneau, Claire Perret, Elisa Yaniz-Galende, Nadia Rosenthal, David-Alexandre Trégouët, Giovanna Marazzi, Jean-Sébastien Silvestre, David Sassoon, Jean-Sébastien Hulot. Anti-integrin αv therapy improves cardiac fibrosis after myocardial infarction by blunting cardiac PW1+ stromal cells. Scientific reports. 2020 Jul 09;10(1):11404
PMID: 32647159
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