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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Article number81
Pages (from-to)81
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 10 Jan 2022

Bibliographical note

Funding Information:
This work was supported by project INCardio funded by the European Regional Development Fund and Interreg V-A Italy-Austria 2014-2020 to S.Z. and M.M. and by the Scientific Center of Excellence for Reproductive and Regenerative Medicine (project “Reproductive and regenerative medicine—exploration of new platforms and potentials” GA KK01.1.1.01.0008 funded by the EU through the ERDF) to S.V.

Publisher Copyright:
© 2022, The Author(s).

Other keywords

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

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