P2Y(4) nucleotide receptor: a novel actor in post-natal cardiac development

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...

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Bibliographic Details
Published in:Angiogenesis (London) 2012-09, Vol.15 (3), p.349-360
Main Authors: Horckmans, Michael, Robaye, Bernard, Léon-Gόmez, Elvira, Lantz, Nicolas, Unger, Philippe, Dol-Gleizes, Frédérique, Clouet, Sophie, Cammarata, Dorothée, Schaeffer, Paul, Savi, Pierre, Gachet, Christian, Balligand, Jean-Luc, Dessy, Chantal, Boeynaems, Jean-Marie, Communi, Didier
Format: Article
Language:English
Subjects:
Animals
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Heart - growth & development
Humans
Immunohistochemistry
Mice
Mice, Knockout
Neovascularization, Physiologic
Receptors, Purinergic P2 - physiology
Reverse Transcriptase Polymerase Chain Reaction
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Summary: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.
ISSN:1573-7209
DOI:10.1007/s10456-012-9265-1