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Angiogenesis

, Volume 15, Issue 3, pp 349–360 | Cite as

P2Y4 nucleotide receptor: a novel actor in post-natal cardiac development

  • Michael Horckmans
  • Bernard Robaye
  • Elvira Léon-Gόmez
  • Nicolas Lantz
  • Philippe Unger
  • Frédérique Dol-Gleizes
  • Sophie Clouet
  • Dorothée Cammarata
  • Paul Schaeffer
  • Pierre Savi
  • Christian Gachet
  • Jean-Luc Balligand
  • Chantal Dessy
  • Jean-Marie Boeynaems
  • Didier CommuniEmail author
Original Paper

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 P2Y4-null mice display microcardia. P2Y4 nucleotide receptor is expressed in cardiac endothelial cells but not in cardiomyocytes. Loss of P2Y4 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 P2Y4-null hearts early after birth, resulting in reduced heart growth. Our study uncovers mouse P2Y4 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 P2Y4 expression in human cardiac microvessels. P2Y4 receptor could constitute a therapeutic target to regulate cardiac remodelling and post-ischemic revascularisation.

Keywords

Heart development Angiogenesis Nucleotides Endothelial cells P2Y receptors 

Notes

Acknowledgments

We thank Larissa di Pietrantonio, Olivier Vosters, Dominique Fokan, Hrag Esfahani and Steven Droogmans for help and technical assistance. The authors are grateful to Dr Andreas Markl for invaluable assistance in telemetry and helpful discussion. This work was supported by an Action de Recherche Concertée of the Communauté Française de Belgique, an Interuniversity Attraction Pole grant from the Politique Scientifique Fédérale (IAP-P6/30), Prime Minister’s Office, Federal Service for Science, Technology and Culture, by grants of the Fonds de la Recherche Scientifique Médicale (F.R.S.M.), the Fonds d’Encouragement à la Recherche (F.E.R.), the Fonds Emile DEFAY, the Fonds de la Recherche Scientifique Médicale of Belgium, the Walloon Region (Programme d’Excellence CIBLES), and the LifeSciHealth programme of the European Community (grant LSHB-2003-503337). D. Communi and C. Dessy are Senior Research Associates of the Fonds National de la Recherche Scientifique (F.N.R.S.). M. Horckmans is supported by the Fonds National de la Recherche Scientifique/FRIA, Belgium. Philippe Unger has received a grant from the “Fonds pour la Chirurgie Cardiaque”, Elvira Leon-Gomez is supported by a grant of the F.S.R. (Fonds Spécial de Recherche) of the U.C.L. (Université catholique de Louvain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Michael Horckmans
    • 1
  • Bernard Robaye
    • 2
  • Elvira Léon-Gόmez
    • 3
  • Nicolas Lantz
    • 4
  • Philippe Unger
    • 5
  • Frédérique Dol-Gleizes
    • 6
  • Sophie Clouet
    • 1
  • Dorothée Cammarata
    • 2
  • Paul Schaeffer
    • 6
  • Pierre Savi
    • 6
  • Christian Gachet
    • 4
  • Jean-Luc Balligand
    • 3
  • Chantal Dessy
    • 3
  • Jean-Marie Boeynaems
    • 1
    • 7
  • Didier Communi
    • 1
    Email author
  1. 1.Institute of Interdisciplinary Research, IRIBHMUniversité Libre de BruxellesBrusselsBelgium
  2. 2.Institute of Interdisciplinary Research, IRIBHMUniversité Libre de BruxellesGosseliesBelgium
  3. 3.Unit of Pharmacology and TherapeuticsUniversité catholique de LouvainBrusselsBelgium
  4. 4.Department Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusionUMR_S949 INSERM-Université de Strasbourg, Etablissement Français du Sang-AlsaceStrasbourgFrance
  5. 5.Department of Cardiology, Erasme HospitalUniversité Libre de BruxellesBrusselsBelgium
  6. 6.Département Thrombose and AngiogenèseService de Pharmacologie, Sanofi-AventisToulouseFrance
  7. 7.Department of Laboratory Medicine, Erasme HospitalUniversité Libre de BruxellesBrusselsBelgium

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