Injectable human recombinant collagen matrices limit adverse remodeling and improve cardiac function after myocardial infarction

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作者
Sarah McLaughlin
Brian McNeill
James Podrebarac
Katsuhiro Hosoyama
Veronika Sedlakova
Gregory Cron
David Smyth
Richard Seymour
Keshav Goel
Wenbin Liang
Katey J. Rayner
Marc Ruel
Erik J. Suuronen
Emilio I. Alarcon
机构
[1] University of Ottawa Heart Institute,BioEngineering and Therapeutic Solutions (BEaTS), Division of Cardiac Surgery
[2] University of Ottawa,Department of Cellular & Molecular Medicine
[3] University of Ottawa,Department of Radiology, Faculty of Medicine
[4] University of Ottawa Heart Institute,Cardiac Function Laboratory
[5] University of Ottawa Heart Institute,Cardiac Electrophysiology Lab
[6] University of Ottawa Heart Institute,Cardiometabolic microRNA Laboratory
[7] University of Ottawa,Department of Biochemistry, Microbiology, and Immunology
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Despite the success of current therapies for acute myocardial infarction (MI), many patients still develop adverse cardiac remodeling and heart failure. With the growing prevalence of heart failure, a new therapy is needed that can prevent remodeling and support tissue repair. Herein, we report on injectable recombinant human collagen type I (rHCI) and type III (rHCIII) matrices for treating MI. Injecting rHCI or rHCIII matrices in mice during the late proliferative phase post-MI restores the myocardium’s mechanical properties and reduces scar size, but only the rHCI matrix maintains remote wall thickness and prevents heart enlargement. rHCI treatment increases cardiomyocyte and capillary numbers in the border zone and the presence of pro-wound healing macrophages in the ischemic area, while reducing the overall recruitment of bone marrow monocytes. Our findings show functional recovery post-MI using rHCI by promoting a healing environment, cardiomyocyte survival, and less pathological remodeling of the myocardium.
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