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

• Published in: Nature communications Vol. 10; no. 1; pp. 4866 - 14
• Main Authors: McLaughlin, Sarah, McNeill, Brian, Podrebarac, James, Hosoyama, Katsuhiro, Sedlakova, Veronika, Cron, Gregory, Smyth, David, Seymour, Richard, Goel, Keshav, Liang, Wenbin, Rayner, Katey J., Ruel, Marc, Suuronen, Erik J., Alarcon, Emilio I.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/107; 14/63; 692/308/575; 692/4019/2773; Animals; Bone marrow; Capillaries - drug effects; Carbodiimides - pharmacology; Cardiomyocytes; Cell Proliferation - drug effects; Cell Survival - drug effects; Cicatrix - pathology; Collagen; Collagen (type I); Collagen Type I - pharmacology; Collagen Type III - pharmacology; Congestive heart failure; Coronary Vessels - drug effects; Cross-Linking Reagents - pharmacology; Dimethylamines - pharmacology; Enlargement; Heart; Heart - drug effects; Heart attacks; Heart failure; Humanities and Social Sciences; Humans; Ischemia; Macrophages; Macrophages - drug effects; Mechanical properties; Mice; Monocytes; Monocytes - drug effects; multidisciplinary; Myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardium; Myocardium - pathology; Myocytes, Cardiac - drug effects; Recombinant Proteins - pharmacology; Recovery of function; Science; Science (multidisciplinary); Succinimides - pharmacology; Ventricular Function - drug effects; Ventricular Remodeling - drug effects; Wall thickness; Wound healing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12748-8

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. Many patients, following therapy for acute myocardial infarction, develop adverse cardiac remodelling. Here the authors present injectable recombinant human collagen 10 of 10 type I and III matrices that are able to limit adverse remodelling and improve function of the myocardium.