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

Tomohiro Yokota | Zendy; Jackie L. McCourt | Zendy; Feiyang Ma | Zendy; Shuxun Ren | Zendy; Shen Li | Zendy; TaeHyung Kim | Zendy; Yerbol Z. Kurmangaliyev | Zendy; Rohollah Nasiri | Zendy; Samad Ahadian | Zendy; Thang L. Nguyen | Zendy; Xing Haw Marvin Tan | Zendy; Yonggang Zhou | Zendy; Rimao Wu | Zendy; A. Domínguez Rodríguez | Zendy; Whitaker Cohn | Zendy; Yibin Wang | Zendy; Julian P. Whitelegge | Zendy; Sergey Ryazantsev | Zendy; Ali Khademhosseini | Zendy; Michael A. Teitell | Zendy; PeiYu Chiou | Zendy; David E. Birk | Zendy; Amy C. Rowat | Zendy; Rachelle H. Crosbie | Zendy; Matteo Pellegrini | Zendy; Marcus M. Seldin | Zendy; Aldons J. Lusis | Zendy; Arjun Deb | Zendy

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

Author(s) -

Tomohiro Yokota,

Jackie L. McCourt,

Feiyang Ma,

Shuxun Ren,

Shen Li,

TaeHyung Kim,

Yerbol Z. Kurmangaliyev,

Rohollah Nasiri,

Samad Ahadian,

Thang L. Nguyen,

Xing Haw Marvin Tan,

Yonggang Zhou,

Rimao Wu,

A. Domínguez Rodríguez,

Whitaker Cohn,

Yibin Wang,

Julian P. Whitelegge,

Sergey Ryazantsev,

Ali Khademhosseini,

Michael A. Teitell,

PeiYu Chiou,

David E. Birk,

Amy C. Rowat,

Rachelle H. Crosbie,

Matteo Pellegrini,

Marcus M. Seldin,

Aldons J. Lusis,

Arjun Deb

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.06.030

Subject(s) - scars , integrin , mechanosensitive channels , collagen receptor , biology , extracellular matrix , collagen vi , myocardial infarction , type i collagen , fibroblast , phenotype , scar tissue , pathology , microbiology and biotechnology , medicine , endocrinology , surgery , cell , in vitro , receptor , genetics , ion channel , gene

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.

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