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

doi:10.1038/s41467-021-27622-9

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

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

22 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 language	English
Article number	81
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27622-9
Publication status	Published - Dec 2022

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Vukicevic, S., Colliva, A., Kufner, V., Martinelli, V., Moimas, S., Vodret, S., Rumenovic, V., Milosevic, M., Brkljacic, B., Delic-Brkljacic, D., Correa, R., Giacca, M., Maglione, M., Bordukalo-Niksic, T., Dumic-Cule, I., & Zacchigna, S. (2022). Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction. Nature Communications, 13(1), Article 81. https://doi.org/10.1038/s41467-021-27622-9

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title = "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.",

author = "Slobodan Vukicevic and Andrea Colliva and Vera Kufner and Valentina Martinelli and Silvia Moimas and Simone Vodret and Viktorija Rumenovic and Milan Milosevic and Boris Brkljacic and Diana Delic-Brkljacic and Ricardo Correa and Mauro Giacca and Manuel Maglione and Tatjana Bordukalo-Niksic and Ivo Dumic-Cule and Serena Zacchigna",

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: {\textcopyright} 2022, The Author(s).",

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Vukicevic, S, Colliva, A, Kufner, V, Martinelli, V, Moimas, S, Vodret, S, Rumenovic, V, Milosevic, M, Brkljacic, B, Delic-Brkljacic, D, Correa, R, Giacca, M, Maglione, M, Bordukalo-Niksic, T, Dumic-Cule, I & Zacchigna, S 2022, 'Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction', Nature Communications, vol. 13, no. 1, 81. https://doi.org/10.1038/s41467-021-27622-9

TY - JOUR

T1 - Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction

AU - Vukicevic, Slobodan

AU - Colliva, Andrea

AU - Kufner, Vera

AU - Martinelli, Valentina

AU - Moimas, Silvia

AU - Vodret, Simone

AU - Rumenovic, Viktorija

AU - Milosevic, Milan

AU - Brkljacic, Boris

AU - Delic-Brkljacic, Diana

AU - Correa, Ricardo

AU - Giacca, Mauro

AU - Maglione, Manuel

AU - Bordukalo-Niksic, Tatjana

AU - Dumic-Cule, Ivo

AU - Zacchigna, Serena

N1 - 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).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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VL - 13

JO - Nature Communications

JF - Nature Communications

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ER -

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

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