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Anti‐apoptotic effects of pioglitazone in hypercholesterolemic rats subjected to myocardial ischemia/reperfusion
Author(s) -
Wu Ye,
Yan Zi,
Wang Xiaoliang,
Tian Jue,
Yang Xiaoli,
Ma Xinliang,
Liu Huirong
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.a1222-a
Objective To investigate the effects of pioglitazone, an agonist of peroxisome proliferator‐activated receptor (PPAR) γ, on postischemic myocardial apoptosis in hypercholesterolemic (HC) rats. Methods Male Wistar rats were fed with normal or high cholesterol diets for 8 weeks. Four weeks after being fed a high cholesterol diet, HC rats were randomized to receive vehicle or pioglitazone during the remaining 4 weeks. At the end of 8 weeks, rats were then subjected to 30 min of coronary occlusion followed by 3 h of reperfusion. The myocardial infarct size, myocardial apoptosis, caspase‐3 activity, nitric oxide (NO) contents and iNOS expression were measured by TTC staining, TUNEL assay, colorimetric assay, nitrate reductase assay and western‐blotting. Results Compared with normal diet, HC had increased the myocardial infarct size (35±2% vs. 56±6%), caspase‐3 activity, apoptotic cell death (15±3% vs. 22±2%), iNOS expression and NO contents (1.27±0.13¦Ìmol/gprot) ( P <0.05). Treatment with pioglitazone in HC rats reduced the ischemia/reperfusion myocardial infarct size (39±2%), attenuated iNOS expression, NO contents (0.80±0.09¦Ìmol/gprot) and myocardial apoptosis (16±1%) ( P <0.05). Conclusion Our results demonstrated that HC increased ischemia/reperfusion injury evidenced by aggravated cardiac dysfunction. In addition, pioglitazone could improve cardiac function and protect the heart injury after myocardial ischemia/reperfusion in HC rats. The PPARγ agonists may protect the heart from subsequent is ischemia/reperfusion‐induced myocardial apoptosis.