title: Loss of Mouse P2Y6 Nucleotide Receptor Is Associated with Physiological Macrocardia and Amplified Pathological Cardiac Hypertrophy.
abstract: The study of the mechanisms leading to cardiac hypertrophy is essential to better understand cardiac development and regeneration. Pathological conditions such as ischemia or pressure overload can induce a release of extracellular nucleotides within the heart. We recently investigated the potential role of nucleotide P2Y receptors in cardiac development. We showed that adult P2Y4-null mice displayed microcardia resulting from defective cardiac angiogenesis. Here we show that loss of another P2Y subtype called P2Y6, a UDP receptor, was associated with a macrocardia phenotype and amplified pathological cardiac hypertrophy. Cardiomyocyte proliferation and size were increased in vivo in hearts of P2Y6-null neonates, resulting in enhanced postnatal heart growth. We then observed that loss of P2Y6 receptor enhanced pathological cardiac hypertrophy induced after isoproterenol injection. We identified an inhibitory effect of UDP on in vitro isoproterenol-induced cardiomyocyte hyperplasia and hypertrophy. The present study identifies mouse P2Y6 receptor as a regulator of cardiac development and cardiomyocyte function. P2Y6 receptor could constitute a therapeutic target to regulate cardiac hypertrophy.
authors.affiliation: From the Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, 1070 Brussels.
authors.forename: Sophie
authors.initials: S
authors.lastname: Clouet
authors.affiliation: From the Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, 1070 Brussels.
authors.forename: Larissa
authors.initials: L
authors.lastname: Di Pietrantonio
authors.affiliation: the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels.
authors.forename: Evangelos-Panagiotis
authors.initials: EP
authors.lastname: Daskalopoulos
authors.affiliation: the Unit of Pharmacology and Therapeutics, Université Catholique de Louvain, UCL-FATH 5349, 1200 Brussels, and.
authors.forename: Hrag
authors.initials: H
authors.lastname: Esfahani
authors.affiliation: From the Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, 1070 Brussels.
authors.forename: Michael
authors.initials: M
authors.lastname: Horckmans
authors.affiliation: From the Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, 1070 Brussels.
authors.forename: Marion
authors.initials: M
authors.lastname: Vanorlé
authors.affiliation: From the Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, 1070 Brussels.
authors.forename: Anne
authors.initials: A
authors.lastname: Lemaire
authors.affiliation: the Unit of Pharmacology and Therapeutics, Université Catholique de Louvain, UCL-FATH 5349, 1200 Brussels, and.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
authors.affiliation: the Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels.
authors.forename: Christophe
authors.initials: C
authors.lastname: Beauloye
authors.affiliation: From the Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, 1070 Brussels, the Department of Laboratory Medicine, Erasme Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boeynaems
authors.affiliation: From the Institute of Interdisciplinary Research, IRIBHM, Université Libre de Bruxelles, 1070 Brussels, communid@ulb.ac.be.
authors.forename: Didier
authors.initials: D
authors.lastname: Communi
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006965:Hyperplasia; D007545:Isoproterenol / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018048:Receptors, Purinergic P2; C104749:purinoceptor P2Y4; C099845:purinoceptor P2Y6; D007545:Isoproterenol
keywords: G protein-coupled receptor (GPCR); P2Y6 receptor; UDP; cardiac hypertrophy; cardiomyocyte; heart development; isoproterenol; nucleotide