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Article Cell ; Volume 182, Issue 3 , 2020 , Pages 545-562.e23 ; McCourt, J ; Ma, F ; Ren, S ; Li, S ; Kim, T. H ; Kurmangaliyev, Y. Z ; Nasiri, R ; Ahadian, S ; Nguyen, T ; Tan, X. H. M ; Zhou, Y ; Wu, R ; Rodriguez, A ; Cohn, W ; Wang, Y ; Whitelegge, J ; Ryazantsev, S ; Khademhosseini, A ; Teitell, M. A ; Chiou, P. Y ; Birk, D. E ; Rowat, A. C ; Crosbie, R. H ; Pellegrini, M ; Seldin, M ; Lusis, A. J ; Deb, A ; Sharif University of Technology
Cell Press 2020
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...