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Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth

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Abstract

Brain natriuretic peptide (BNP) contributes to heart formation during embryogenesis. After birth, despite a high number of studies aimed at understanding by which mechanism(s) BNP reduces myocardial ischemic injury in animal models, the actual role of this peptide in the heart remains elusive. In this study, we asked whether BNP treatment could modulate the proliferation of endogenous cardiac progenitor cells (CPCs) and/or their differentiation into cardiomyocytes. CPCs expressed the NPR-A and NPR-B receptors in neonatal and adult hearts, suggesting their ability to respond to BNP stimulation. BNP injection into neonatal and adult unmanipulated mice increased the number of newly formed cardiomyocytes (neonatal: +23 %, p = 0.009 and adult: +68 %, p = 0.0005) and the number of proliferating CPCs (neonatal: +142 %, p = 0.002 and adult: +134 %, p = 0.04). In vitro, BNP stimulated CPC proliferation via NPR-A and CPC differentiation into cardiomyocytes via NPR-B. Finally, as BNP might be used as a therapeutic agent, we injected BNP into mice undergoing myocardial infarction. In pathological conditions, BNP treatment was cardioprotective by increasing heart contractility and reducing cardiac remodelling. At the cellular level, BNP stimulates CPC proliferation in the non-infarcted area of the infarcted hearts. In the infarcted area, BNP modulates the fate of the endogenous CPCs but also of the infiltrating CD45+ cells. These results support for the first time a key role for BNP in controlling the progenitor cell proliferation and differentiation after birth. The administration of BNP might, therefore, be a useful component of therapeutic approaches aimed at inducing heart regeneration.

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Abbreviations

BNP:

Brain natriuretic peptide

BrdU:

5-Bromo-2′-deoxyuridine

CPCs:

Cardiac progenitor cells

GFP:

Green fluorescent protein

NMCs:

Non-myocyte cells

NPR-A:

Natriuretic peptide receptor A

NPR-B:

Natriuretic peptide receptor B

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Acknowledgments

The authors thank Ms Catherine Pythoud for her helpful work and Mr Alexandre Sarre for his technical expertise. This work is supported by a grant from the Swiss National Science Foundation.(PMPDB-310030-_132491).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All animal studies have been approved by the appropriate ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The manuscript does not contain clinical studies or patient data.

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Authors and Affiliations

  1. Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Bugnon 7a, 1005, Lausanne, Switzerland

    Christelle Bielmann, Stéphanie Rignault-Clerc, Tamara Zehnder, Bernard Waeber, François Feihl & Nathalie Rosenblatt-Velin

  2. Service de Médecine Intensive Adulte, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

    Lucas Liaudet

  3. Department of Pathology and Laboratory Medecine, University of North Carolina, Chapel Hill, Wilmington, NC, USA

    Feng Li

  4. Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan

    Tetsuo Kunieda

  5. Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan

    Chizuru Sogawa

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  1. Christelle Bielmann
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  2. Stéphanie Rignault-Clerc
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  3. Lucas Liaudet
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  4. Feng Li
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  5. Tetsuo Kunieda
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  7. Tamara Zehnder
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  8. Bernard Waeber
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  9. François Feihl
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  10. Nathalie Rosenblatt-Velin
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Correspondence to Nathalie Rosenblatt-Velin.

Additional information

C. Bielmann and S. Rignault-Clerc contributed equally to this work.

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Bielmann, C., Rignault-Clerc, S., Liaudet, L. et al. Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth. Basic Res Cardiol 110, 455 (2015). https://doi.org/10.1007/s00395-014-0455-4

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