Document Type
Article
Publication Date
7-9-2020
Keywords
JMG
JAX Source
Sci Rep 2020 Jul 9; 10(1):11404
PMID
32647159
DOI
https://doi.org/10.1038/s41598-020-68223-8
Abstract
There 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.
Recommended Citation
Bouvet, Marion; Claude, Olivier; Roux, Maguelonne; Skelly, Daniel A; 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; and Hulot, Jean-Sébastien, "Anti-integrin αv therapy improves cardiac fibrosis after myocardial infarction by blunting cardiac PW1+ stromal cells." (2020). Faculty Research 2020. 135.
https://mouseion.jax.org/stfb2020/135
Comments
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