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

Yerbol Kurmangaliyev; Tomohiro Yokota; Jackie L McCourt; Feiyang Ma; Shuxun Ren; Shen Li; Tae-Hyung Kim; Rohollah Nasiri; Samad Ahadian; Thang Nguyen; Xing Haw Marvin Tan; Yonggang Zhou; Rimao Wu; Abraham Rodriguez; Whitaker Cohn; Yibin Wang; Julian Whitelegge; Sergey Ryazantsev; Ali Khademhosseini; Michael A. Teitell; Pei-Yu Chiou; David E. Birk; Amy C. Rowat; Rachelle H. Crosbie; Matteo Pellegrini; Marcus Seldin; Aldons J. Lusis; Arjun Deb

doi:10.1016/j.cell.2020.06.030

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

Journal article

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

Yerbol Kurmangaliyev, Tomohiro Yokota, Jackie L McCourt, Feiyang Ma, Shuxun Ren, Shen Li, Tae-Hyung Kim, Rohollah Nasiri, Samad Ahadian, Thang Nguyen, …

Cell, Vol.182(3), pp.545-562.e23

08/06/2020

DOI: https://doi.org/10.1016/j.cell.2020.06.030

PMID: 32621799

Abstract

Biochemistry & Molecular Biology

Life Sciences & Biomedicine

Science & Technology

Cell Biology

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, aminor 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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Title: Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury
Creators: Yerbol Kurmangaliyev
Tomohiro Yokota - Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA
Jackie L McCourt - Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA
Feiyang Ma - Univ Calif Los Angeles, Coll Letters & Sci, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
Shuxun Ren - Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA
Shen Li - Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA
Tae-Hyung Kim - Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA
Rohollah Nasiri - Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
Samad Ahadian - Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
Thang Nguyen - Univ Calif Los Angeles, Sch Engn, Dept Bioengn, Los Angeles, CA 90095 USA
Xing Haw Marvin Tan - Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
Yonggang Zhou - Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA
Rimao Wu - Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA
Abraham Rodriguez - Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA
Whitaker Cohn - David Geffen Sch Med, Semel Inst Neurosci & Behav, Passarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA
Yibin Wang - Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA
Julian Whitelegge - David Geffen Sch Med, Semel Inst Neurosci & Behav, Passarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA
Sergey Ryazantsev - Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
Ali Khademhosseini - Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
Michael A. Teitell - Univ Calif Los Angeles, Sch Engn, Dept Bioengn, Los Angeles, CA 90095 USA
Pei-Yu Chiou - Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA
David E. Birk - Univ S Florida, Coll Med, Tampa, FL 33612 USA
Amy C. Rowat - Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA
Rachelle H. Crosbie - Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA
Matteo Pellegrini - Univ Calif Los Angeles, Coll Letters & Sci, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
Marcus Seldin - Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA
Aldons J. Lusis - Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA
Arjun Deb - Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA
Publication Details: Cell, Vol.182(3), pp.545-562.e23
Publisher: Elsevier
Identifiers: 9924209575501921
Academic Unit: Department of Biology
Language: English
Resource Type: Journal article

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

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