title: Up-regulation of hypoxia-inducible factor-1α enhanced the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats.
abstract: Hyperlipidemia is an independent risk factor in the development of ischemic heart disease, which can increase myocardial susceptibility to ischemia/reperfusion (I/R) injury. Ischemic postconditioning (PostC) has now been demonstrated as a novel strategy to harness nature's protection against myocardial I/R injury in normal conditions. However, the effect of PostC on hyperlipidemic animals remains elusive. It has been shown in our previous study that PostC reduces the myocardial I/R injury, and hypoxia-inducible factor-1α (HIF-1α) may play an important role in the cardioprotective mechanisms of PostC on normal rats. Here, we tested the hypothesis that the cardioprotection of PostC on hyperlipidemic rats is associated with the up-regulated HIF-1α expression. Male Wistar rats were fed with a high-fat diet for 8 weeks, and then randomly divided into five groups: sham, I/R, dimethyloxalylglycine (DMOG) + I/R, PostC, and DMOG + PostC group. The detrimental indices induced by I/R injury included infarct size, plasma creatine kinase (CK) activity and caspase-3 activity. The results showed that PostC could reduce the infarct size, when compared with the I/R group, which was consistent with the significant lower levels of plasma CK activity and caspase-3 activity, and that it increased the expression of HIF-1α in hyperlipidemic rats. When DMOG was given before PostC to up-regulate HIF-1α protein level, the degree of I/R injury was attenuated. In conclusion, these data suggested that the up-regulation of HIF-1α may be one of the cardioprotective mechanisms of PostC against I/R injury in hyperlipidemic rats.
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Huanxin
authors.initials: H
authors.lastname: Zhao
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Suli
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Huirong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000627:therapeutic use; D000818:Animals; D059305:Diet, High-Fat; D006949:Hyperlipidemias / Q000150:complications; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D057775:Ischemic Postconditioning; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D000600:Amino Acids, Dicarboxylic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C040947:oxalylglycine
keywords: DMOG; hyperlipidemia; hypoxia-inducible factor-1; ischemic postconditioning