Role of P2X purinergic receptors in the rescue of ischemic heart failure.
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.
Sonin
Dmitry
D
Pat and Jim Calhoun Cardiology Ctr., MC-3946, Univ. of Connecticut Health Ctr., 263 Farmington Ave., Farmington, CT 06030, USA.
Zhou
Si-Yuan
SY
Cronin
Chunxia
C
Sonina
Tatiana
T
Wu
Jeffrey
J
Jacobson
Kenneth A
KA
Pappano
Achilles
A
Liang
Bruce T
BT
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
C548227:P2rx4 protein, mouse; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4