title: P2Y(4) nucleotide receptor: a novel actor in post-natal cardiac development.
abstract: Communication between endothelial cells and cardiomyocytes is critical for cardiac development and regeneration. However the mechanisms involved in these endothelial-cardiomyocyte interactions remain poorly understood. Nucleotides are released within the heart, especially under ischemia or pressure overload. The function of P2Y nucleotide receptors in cardiac development has never been investigated. Here we show that adult P2Y(4)-null mice display microcardia. P2Y(4) nucleotide receptor is expressed in cardiac endothelial cells but not in cardiomyocytes. Loss of P2Y(4) in cardiac endothelial cells strongly inhibits their growth, migration and PDGF-B secretion in response to UTP. Proliferation of microvessels and cardiomyocytes is reduced in P2Y(4)-null hearts early after birth, resulting in reduced heart growth. Our study uncovers mouse P2Y(4) receptor as an essential regulator of cardiac endothelial cell function, and illustrates the involvement of endothelial-cardiomyocyte interactions in post-natal heart development. We also detected P2Y(4) expression in human cardiac microvessels. P2Y(4) receptor could constitute a therapeutic target to regulate cardiac remodelling and post-ischemic revascularisation.
authors.affiliation: Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, Building C (5th floor), Campus Erasme, 808 Route de Lennik, 1070, Brussels, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Horckmans
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaye
authors.forename: Elvira
authors.initials: E
authors.lastname: Léon-Gόmez
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lantz
authors.forename: Philippe
authors.initials: P
authors.lastname: Unger
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dol-Gleizes
authors.forename: Sophie
authors.initials: S
authors.lastname: Clouet
authors.forename: Dorothée
authors.initials: D
authors.lastname: Cammarata
authors.forename: Paul
authors.initials: P
authors.lastname: Schaeffer
authors.forename: Pierre
authors.initials: P
authors.lastname: Savi
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
authors.forename: Chantal
authors.initials: C
authors.lastname: Dessy
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boeynaems
authors.forename: Didier
authors.initials: D
authors.lastname: Communi
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006321:Heart / Q000254:growth & development*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018048:Receptors, Purinergic P2; C104749:purinoceptor P2Y4