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

Sci Rep. 2020 Jul 9;10(1):11404. doi: 10.1038/s41598-020-68223-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Fibrosis
  • Integrin alphaV / drug effects*
  • Integrin alphaV / physiology
  • Kruppel-Like Transcription Factors / analysis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • RNA, Messenger / biosynthesis
  • Single-Cell Analysis
  • Snake Venoms / pharmacology
  • Snake Venoms / therapeutic use*
  • Stromal Cells / chemistry
  • Stromal Cells / drug effects*
  • Transforming Growth Factor beta1 / pharmacology


  • Integrin alphaV
  • Kruppel-Like Transcription Factors
  • Peg3 protein, mouse
  • RNA, Messenger
  • Snake Venoms
  • Transforming Growth Factor beta1
  • Cilengitide