Loss of Mouse P2Y6 Nucleotide Receptor Is Associated with Physiological Macrocardia and Amplified Pathological Cardiac Hypertrophy

被引:22
|
作者
Clouet, Sophie [1 ]
Di Pietrantonio, Larissa [1 ]
Daskalopoulos, Evangelos-Panagiotis [2 ]
Esfahani, Hrag [3 ]
Horckmans, Michael [1 ]
Vanorle, Marion [1 ]
Lemaire, Anne [1 ]
Balligand, Jean-Luc [3 ]
Beauloye, Christophe [2 ]
Boeynaems, Jean-Marie [1 ,4 ]
Communi, Didier [1 ]
机构
[1] Univ Libre Bruxelles, IRIBHM, Inst Interdisciplinary Res, B-1070 Brussels, Belgium
[2] Catholic Univ Louvain, Inst Rech Expt & Clin, Pole Cardiovasc Res, B-1200 Brussels, Belgium
[3] Catholic Univ Louvain, Unit Pharmacol & Therapeut, UCL FATH 5349, B-1200 Brussels, Belgium
[4] Univ Libre Bruxelles, Erasme Hosp, Dept Lab Med, B-1070 Brussels, Belgium
关键词
UTP REDUCES INFARCT; MYOCARDIAL HYPERTROPHY; KNOCKOUT MICE; NATRIURETIC PEPTIDES; HEART FUNCTION; RAT-HEART; CARDIOMYOCYTES; EXPRESSION; ISCHEMIA; PROTEINS;
D O I
10.1074/jbc.M115.684118
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 P2Y(4)-null mice displayed microcardia resulting from defective cardiac angiogenesis. Here we show that loss of another P2Y subtype called P2Y(6), 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 P2Y(6)-null neonates, resulting in enhanced postnatal heart growth. We then observed that loss of P2Y(6) 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 P2Y(6) receptor as a regulator of cardiac development and cardiomyocyte function. P2Y(6) receptor could constitute a therapeutic target to regulate cardiac hypertrophy.
引用
收藏
页码:15841 / 15852
页数:12
相关论文
共 50 条
  • [41] The expression of the P2Y6 receptor is regulated at the transcriptional level by p53
    Molle, Caroline M.
    Arguin, Guillaume
    Jemfer, Charlotte
    Placet, Morgane
    Bellefeuille, Steve Dagenais
    Gendron, Fernand-Pierre
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2020, 524 (04) : 798 - 802
  • [42] P2Y6 receptor-dependent microglial phagocytosis of synapses mediates synaptic and memory loss in aging
    Dundee, Jacob M.
    Puigdellivol, Mar
    Butler, Richard
    Cockram, Thomas O. J.
    Brown, Guy C.
    AGING CELL, 2023, 22 (02)
  • [43] Purinergic P2Y6 receptor antagonists as potential anti tumor agents
    Ghimeray, Khagendra
    Sharma, Shilpa
    Akundi, Ravi Shankar
    CANCER RESEARCH, 2024, 84 (06)
  • [44] Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone
    Kauffenstein, Gilles
    Tamareille, Sophie
    Prunier, Fabrice
    Roy, Charlotte
    Ayer, Audrey
    Toutain, Bertrand
    Billaud, Marie
    Isakson, Brant E.
    Grimaud, Linda
    Loufrani, Laurent
    Rousseau, Pascal
    Abraham, Pierre
    Procaccio, Vincent
    Monyer, Hannah
    de Wit, Cor
    Boeynaems, Jean-Marie
    Robaye, Bernard
    Kwak, Brenda R.
    Henrion, Daniel
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2016, 36 (08) : 1598 - 1606
  • [45] The expression of P2Y6 receptor promotes the quality of mucus in colitic mice
    Placet, Morgane
    Molle, Caroline M.
    Arguin, Guillaume
    Geha, Sameh
    Gendron, Fernand-Pierre
    FEBS JOURNAL, 2021, 288 (18) : 5459 - 5473
  • [46] The purinergic receptor P2Y6 contributes to airway inflammation and remodeling in asthma
    Vieira, de Paula R.
    Mueller, T.
    von Gernler, V
    Grimm, M.
    Duerk, T.
    Cicko, S.
    Ayata, C.
    Sorichter, S.
    Robaye, B.
    Zeiser, R.
    Ferrari, D.
    Virchow, J.
    Boeynaems, J.
    Idzko, M.
    ALLERGY, 2011, 66 : 88 - 88
  • [47] DYSREGULATED P2Y6 RECEPTOR SIGNALING INCREASES A RISK FOR PATHOGENESIS OF GLAUCOMA
    Shinozaki, Youichi
    Kashiwagi, Kenji
    Namekata, Kazuhiko
    Ohno, Nobuhiko
    Takeda, Akiko
    Harada, Takayuki
    Iwata, Takeshi
    Koizumi, Schuichi
    PURINERGIC SIGNALLING, 2018, 14 : S93 - S94
  • [48] Potent P2Y6 receptor mediated contractions in human cerebral arteries
    Edvinsson, L
    Malmsjö, M
    Hou, MY
    Pendergast, W
    Erlinge, D
    CEPHALALGIA, 2003, 23 (07) : 695 - 695
  • [49] Functionalized Congeners of 2H-Chromene P2Y6 Receptor Antagonists
    Oliva, Paola
    Pramanik, Asmita
    Jung, Young-Hwan
    Lewicki, Sarah A.
    Mwendwa, Jamie M.
    Park, Jong Hwan
    Jacobson, Kenneth A.
    CELLS, 2024, 13 (16)
  • [50] TLR2-DEPENDENT P2Y6 RECEPTOR MEDIATES THE NEUROPATHIC PAIN
    Park, C.
    Lee, S. Y.
    Lee, S. J.
    JOURNAL OF NEUROCHEMISTRY, 2009, 110 : 108 - 108