Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction
Slobodan Vukičević, Andrea Colliva, Vera Kufner, Valentina Martinelli, Silvia Moimas, Simone Vodret, Viktorija Rumenović, Milan Milošević, Boris Brkljačić, Diana Delić-Brkljačić, Ricardo Correa, Mauro Giacca, Manuel Maglione, Tatjana Bordukalo-Nikšić, Ivo Dumić-Čule, Serena Zacchigna
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.