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
  • [31] P2Y6 nucleotide receptor mediates monocyte interleukin-8 production in response to UDP or lipopolysaccharide
    Warny, M
    Aboudola, S
    Robson, SC
    Sévigny, J
    Communi, D
    Soltoff, SP
    Kelly, CP
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (28) : 26051 - 26056
  • [32] The role of P2Y6 receptor in the pathogenesis of cardiovascular and inflammatory diseases
    Nishiyama, Kazuhiro
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2024, 154 (02) : 108 - 112
  • [33] A role for P2Y6 receptor in regulation of islet hormone release
    Parandeh, Fariborz
    Amisten, Stefan
    Meidute, Sandra
    Erlinge, David
    Salehi, Albert
    PURINERGIC SIGNALLING, 2008, 4 : S50 - S50
  • [34] P2Y6 purinergic receptor as a molecular switch of essential hypertension
    Daghbouche Rubio, Nuria
    Alvarez-Miguel, Ines
    Rojo-Mencia, Jorge
    Alonso, Esperanza
    Cidad, Pilar
    Perez-Garcia, M. Teresa
    Lopez-Lopez, Jose R.
    JOURNAL OF VASCULAR RESEARCH, 2023, 60 (SUPP1) : 50 - 50
  • [35] Microglia P2Y6 receptor is related to Parkinson's disease
    Yang, Xiaodong
    Lou, Yue
    Wang, Xueping
    Liu, Guidong
    Qian, Yiwei
    Ding, Jianqing
    Chen, Shengdi
    Xiao, Qin
    MOVEMENT DISORDERS, 2016, 31 : S60 - S61
  • [36] The microglial P2Y6 receptor as a therapeutic target for neurodegenerative diseases
    Dundee, Jacob M.
    Brown, Guy C.
    TRANSLATIONAL NEURODEGENERATION, 2024, 13 (01):
  • [37] Identification of uracil recognition domains in the rat P2Y6 receptor:: A P2Y1/6 chimeric receptor approach
    Hoffmann, C
    Soltysiak, K
    West, P
    Barak, D
    Jacobson, KA
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2001, 363 (04) : R18 - R18
  • [38] Purinergic receptor Y6 (P2Y6) deficiency impairs left ventricular function
    Ahmed, I.
    Merz, J.
    Dimanski, D.
    Rofa, K.
    Rog-Zielinska, E. A.
    Koentges, C.
    Hoppe, N.
    Dufner, B.
    Kohl, P.
    Bugger, H.
    Hilgendorf, I.
    Bode, C.
    Zirlik, A.
    Stachon, P.
    EUROPEAN HEART JOURNAL, 2019, 40 : 3948 - 3948
  • [39] Expression changes of P2Y2 and P2Y6 nucleotide receptors during C6 glioma cell differentiation
    Garcia, Jose O.
    Angler, Yesseinia
    Cruz, Alexandra
    Aquino, Edna E.
    Gonzalez, Fernando A.
    Silva, Walter I.
    FASEB JOURNAL, 2007, 21 (06): : A1211 - A1211
  • [40] Increase of P2Y6 gene expression is associated to higher cardiorespiratory capacity in a model of COPD with right ventricular hypertrophy
    Mendez, Andrea
    Garcia, Aline
    Fonseca, Marcelo
    Henriquez, Mauricio
    RESPIROLOGY, 2023, 28 : 294 - 294