Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction

Nat Commun. 2022 Jan 10;13(1):81. doi: 10.1038/s41467-021-27622-9.

Abstract

Despite the high prevalence of ischemic heart diseases worldwide, no antibody-based treatment currently exists. Starting from the evidence that a specific isoform of the Bone Morphogenetic Protein 1 (BMP1.3) is particularly elevated in both patients and animal models of myocardial infarction, here we assess whether its inhibition by a specific monoclonal antibody reduces cardiac fibrosis. We find that this treatment reduces collagen deposition and cross-linking, paralleled by enhanced cardiomyocyte survival, both in vivo and in primary cultures of cardiac cells. Mechanistically, we show that the anti-BMP1.3 monoclonal antibody inhibits Transforming Growth Factor β pathway, thus reducing myofibroblast activation and inducing cardioprotection through BMP5. Collectively, these data support the therapeutic use of anti-BMP1.3 antibodies to prevent cardiomyocyte apoptosis, reduce collagen deposition and preserve cardiac function after ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Bone Morphogenetic Protein 1 / antagonists & inhibitors
  • Bone Morphogenetic Protein 1 / genetics*
  • Bone Morphogenetic Protein 1 / metabolism
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Morphogenetic Protein 5 / genetics
  • Bone Morphogenetic Protein 5 / metabolism
  • Cardiotonic Agents / pharmacology*
  • Case-Control Studies
  • Cell Survival / drug effects
  • Cicatrix / etiology
  • Cicatrix / genetics*
  • Cicatrix / metabolism
  • Cicatrix / prevention & control
  • Disease Models, Animal
  • Endomyocardial Fibrosis / etiology
  • Endomyocardial Fibrosis / genetics*
  • Endomyocardial Fibrosis / metabolism
  • Endomyocardial Fibrosis / prevention & control
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / complications
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / metabolism
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Primary Cell Culture
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Troponin T / genetics
  • Troponin T / metabolism

Substances

  • Antibodies, Monoclonal
  • BMP2 protein, human
  • BMP5 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 5
  • Cardiotonic Agents
  • Protein Isoforms
  • Transforming Growth Factor beta
  • Troponin T
  • BMP1 protein, human
  • Bone Morphogenetic Protein 1