| Literature DB >> 32621799 |
Tomohiro Yokota1, Jackie McCourt2, Feiyang Ma3, Shuxun Ren4, Shen Li1, Tae-Hyung Kim2, Yerbol Z Kurmangaliyev5, Rohollah Nasiri6, Samad Ahadian7, Thang Nguyen8, Xing Haw Marvin Tan9, Yonggang Zhou1, Rimao Wu1, Abraham Rodriguez1, Whitaker Cohn10, Yibin Wang4, Julian Whitelegge10, Sergey Ryazantsev11, Ali Khademhosseini12, Michael A Teitell13, Pei-Yu Chiou9, David E Birk14, Amy C Rowat15, Rachelle H Crosbie16, Matteo Pellegrini3, Marcus Seldin17, Aldons J Lusis18, Arjun Deb19.
Abstract
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.Entities:
Keywords: Col5a1; cilengitide; collagen V; fibrosis; heart scar; integrins; scar mechanics
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Year: 2020 PMID： 32621799 PMCID： PMC7415659 DOI： 10.1016/j.cell.2020.06.030
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850