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Type V collagen in scar tissue regulates the size of scar after heart injury

Yokota, T ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.1016/j.cell.2020.06.030
  3. Publisher: Cell Press , 2020
  4. Abstract:
  5. 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. © 2020 Elsevier Inc
  6. Keywords:
  7. Cilengitide ; Col5a1 ; Collagen V ; Fibrosis ; Heart scar ; Integrins ; Scar mechanics ; Collagen type 1 ; Collagen type 1a1 ; Collagen type 3 ; Collagen type 3a1 ; Collagen type 5 ; Collagen type 5a1 ; Integrin ; Unclassified drug ; Animal cell ; Animal experiment ; Animal model ; Animal tissue ; Cell activation ; Collagen defect ; Controlled study ; Extracellular matrix ; Female ; Fibroblast ; Gene mutation ; Genetic disorder ; Heart fibroblast ; Heart function ; Heart infarction size ; Heart muscle ischemia ; Male ; Mechanotransduction ; Mouse ; Nonhuman ; Phenotype ; Priority journal ; Protein depletion ; Protein expression ; Protein function ; Scar tissue ; Wound healing
  8. Source: Cell ; Volume 182, Issue 3 , 2020 , Pages 545-562.e23
  9. URL: https://pubmed.ncbi.nlm.nih.gov/32621799