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

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.

• Authors: Slobodan Vukicevic, Andrea Colliva, Vera Kufner, Valentina Martinelli, Silvia Moimas, Simone Vodret, Viktorija Rumenovic, Milan Milosevic, Boris Brkljacic, Diana Delic-Brkljacic, Ricardo Correa, Mauro Giacca, Manuel Maglione, Tatjana Bordukalo-Niksic, Ivo Dumic-Cule, Serena Zacchigna
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 81 (01 10 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35013172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• 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

Topics

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