Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury.

Journal Article (Journal Article)

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.

Full Text

Duke Authors

Cited Authors

  • Yokota, T; McCourt, J; Ma, F; Ren, S; Li, S; Kim, T-H; Kurmangaliyev, YZ; Nasiri, R; Ahadian, S; Nguyen, T; Tan, XHM; Zhou, Y; Wu, R; Rodriguez, A; Cohn, W; Wang, Y; Whitelegge, J; Ryazantsev, S; Khademhosseini, A; Teitell, MA; Chiou, P-Y; Birk, DE; Rowat, AC; Crosbie, RH; Pellegrini, M; Seldin, M; Lusis, AJ; Deb, A

Published Date

  • August 6, 2020

Published In

Volume / Issue

  • 182 / 3

Start / End Page

  • 545 - 562.e23

PubMed ID

  • 32621799

Pubmed Central ID

  • PMC7415659

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2020.06.030


  • eng

Conference Location

  • United States