Anti-integrin ?v therapy improves cardiac fibrosis after myocardial infarction by blunting cardiac PW1+ stromal cells.

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 ?V-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 ?V-integrin (CD51) was expressed in almost all cardiac PW1+ cells (93%?±?1%), predominantly as the ?V?1 complex. ?V-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 (TGF? at the surface of cardiac PW1+ cells. Pharmacological inhibition of ?V-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 ?V-integrin could reduce pathological outcomes following cardiac ischemia.

SUBMITTER: Bouvet M 

PROVIDER: S-EPMC7347632 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature