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Publication : Role of P2X purinergic receptors in the rescue of ischemic heart failure.

First Author  Sonin D Year  2008
Journal  Am J Physiol Heart Circ Physiol Volume  295
Issue  3 Pages  H1191-H1197
PubMed ID  18641271 Mgi Jnum  J:141284
Mgi Id  MGI:3817849 Doi  10.1152/ajpheart.00577.2008
Citation  Sonin D, et al. (2008) Role of P2X purinergic receptors in the rescue of ischemic heart failure. Am J Physiol Heart Circ Physiol 295(3):H1191-H1197
abstractText  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.
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