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

Christelle Bielmann, Stéphanie Rignault-Clerc, Lucas Liaudet, Feng Li, Tetsuo Kunieda, Chizuru Sogawa, Tamara Zehnder, Bernard Waeber, François Feihl, Nathalie Rosenblatt-Velin

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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.

Original languageEnglish
JournalBasic Research in Cardiology
Volume110
Issue number1
DOIs
Publication statusPublished - 2015

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Keywords

  • Brain natriuretic peptide
  • Cardiac progenitor cells
  • Cardiomyocytes
  • Differentiation
  • Heart regeneration
  • Natriuretic peptide receptor
  • Proliferation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology
  • Medicine(all)

Cite this

Bielmann, C., Rignault-Clerc, S., Liaudet, L., Li, F., Kunieda, T., Sogawa, C., Zehnder, T., Waeber, B., Feihl, F., & Rosenblatt-Velin, N. (2015). Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth. Basic Research in Cardiology, 110(1). https://doi.org/10.1007/s00395-014-0455-4