title: Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth.
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.
authors.affiliation: Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Bugnon 7a, 1005, Lausanne, Switzerland.
authors.forename: Christelle
authors.initials: C
authors.lastname: Bielmann
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rignault-Clerc
authors.forename: Lucas
authors.initials: L
authors.lastname: Liaudet
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kunieda
authors.forename: Chizuru
authors.initials: C
authors.lastname: Sogawa
authors.forename: Tamara
authors.initials: T
authors.lastname: Zehnder
authors.forename: Bernard
authors.initials: B
authors.lastname: Waeber
authors.forename: François
authors.initials: F
authors.lastname: Feihl
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rosenblatt-Velin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D020097:Natriuretic Peptide, Brain; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A