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

Nat Commun. 2019 Oct 25;10(1):4866. doi: 10.1038/s41467-019-12748-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillaries / drug effects
  • Carbodiimides / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cicatrix / pathology
  • Collagen Type I / pharmacology*
  • Collagen Type III / pharmacology*
  • Coronary Vessels / drug effects
  • Cross-Linking Reagents / pharmacology
  • Dimethylamines / pharmacology
  • Heart / drug effects*
  • Humans
  • Macrophages / drug effects
  • Mice
  • Monocytes / drug effects
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / physiopathology
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Recombinant Proteins / pharmacology*
  • Succinimides / pharmacology
  • Ventricular Function / drug effects*
  • Ventricular Remodeling / drug effects*

Substances

  • Carbodiimides
  • Collagen Type I
  • Collagen Type III
  • Cross-Linking Reagents
  • Dimethylamines
  • N-ethyl-N'-(3-(dimethylamino)-propyl)carbodiimide
  • Recombinant Proteins
  • Succinimides
  • N-hydroxysuccinimide

Grants and funding