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.
Highlights
Despite the high prevalence of ischemic heart diseases worldwide, no antibody-based treatment currently exists
To explore the involvement of BMP1.3 in cardiac fibrosis, we exploited our in house-developed ELISA to quantify BMP1.3 levels in the plasma of either healthy individuals or patients who experienced a recent myocardial infarction (MI), as diagnosed by ST-elevation at electrocardiography and increased troponin T concentration
We show for the first time that a monoclonal antibody inhibiting BMP1.3 reduces collagen deposition, protects cardiomyocytes from ischemic damage and preserves cardiac function following MI
Summary
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 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. Monoclonal antibodies represent the most successful example of biological drugs, which are offering hope for the treatment of various complex disorders, including rheumatological diseases and cancer, and they feed the fastest growing sector in the pharmaceutical industry
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