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Cardiac‐specific Overexpression of Human P2X4 Purinergic Receptors Confers a Beneficial Effect in Left Anterior Descending Artery Ligation Model of Ischemic Cardiomyopathy
Author(s) -
Sonin Dmitry,
Zheng JingGang,
Cronin Chunxia,
Sonina Tatiana,
Liang Bruce
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a800-b
Subject(s) - cardiology , medicine , ligation , cardiac function curve , cardiomyopathy , heart failure , ischemic cardiomyopathy , endocrinology , ejection fraction
P2X receptors are ion channels activated by extracellular ATP. P2X4 receptor (P2X4R) is a subunit of the native cardiac P2XR (FASEB J 20:–284, 2006). Transgenic overexpression of P2X4R (TG) increased lifespan and decreased cardiac hypertrophy in the calsequestrin model of heart failure (Am. J. Physiol. 287:–H1103, 2004). The objective here was to determine the role of cardiac P2XR in the left anterior descending artery (LAD) ligated ischemic cardiomyopathic mice. Permanent LAD ligation without reperfusion resulted in similar infarct (MI) size in TG and NTG (36.4 ± 11%, n=17 mice vs. 41 ± 10%, n=18, respectively, P>0.1). However, TG showed greater LV developed pressure (LVDP) and ±dP/dt, and lower heart weight/body weight ratio and smaller myocyte cross section area than did NTG 7 days after MI (Table, P<0.05 in all comparisons). Two months after MI, the TG showed a greater extent of posterior wall thickening during systole than did NTG (an increase in wall thickness of 0.115 ± 0.012 mm vs. that in NTG of 0.042 ± 0.02 mm, P=0.005), suggesting an improved function in the non‐infarcted area. TG had a lower mortality after MI than NTG (Log rank test, P=0.0047), due to a lower incidence of death in the first 7 days after MI. CONCLUSION: Cardiac‐specific overexpression of the P2X4R can resuce the LAD ligation model of ischemic cardiomyopathy. The beneficial effect was seen 7 days after MI and was sustained for at least two months. The data demonstrate for the first time a novel therapeutic role of this receptor in ischemic heart failure.