title: Role of P2X purinergic receptors in the rescue of ischemic heart failure.
abstract: Evidence is accumulating to support the presence of P2X purinergic receptors in the heart. However, the biological role of this receptor remains to be defined. The objectives here were to determine the role of cardiac P2X receptors in modulating the progression of post-myocardial infarction ischemic heart failure and to investigate the underlying mechanism. The P2X4 receptor (P2X4R) is an important subunit of native cardiac P2X receptors, and the cardiac-specific transgenic overexpression of P2X4R (Tg) was developed as a model. Left anterior descending artery ligation resulted in similar infarct size between Tg and wild-type (WT) mice (P > 0.1). However, Tg mice showed an enhanced cardiac contractile performance at 7 days, 1 mo, and 2 mo after infarction and an increased survival at 1 and 2 mo after infarction (P < 0.01). The enhanced intact heart function was manifested by a greater global left ventricular developed pressure and rate of contraction of left ventricular pressure in vitro and by a significantly increased fractional shortening and systolic thickening in the noninfarcted region in vivo (P < 0.05). The salutary effects on the ischemic heart failure phenotype were seen in both sexes and were not the result of any difference in infarct size in Tg versus WT hearts. An enhanced contractile function of the noninfarcted area in the Tg heart was likely an important rescuing mechanism. The cardiac P2X receptor is a novel target to treat post-myocardial infarction ischemic heart failure.
authors.affiliation: Pat and Jim Calhoun Cardiology Ctr., MC-3946, Univ. of Connecticut Health Ctr., 263 Farmington Ave., Farmington, CT 06030, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Sonin
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
authors.forename: Chunxia
authors.initials: C
authors.lastname: Cronin
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sonina
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wu
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Achilles
authors.initials: A
authors.lastname: Pappano
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Liang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D006334:Heart Function Tests; D006339:Heart Rate / Q000502:physiology; D008026:Ligation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000502:physiology*; D058848:Receptors, Purinergic P2X4; D014463:Ultrasonography
chemical_list: C548227:P2rx4 protein, mouse; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4