| Attenuation of myocardial injury by postconditioning: role of hypoxia inducible factor-1alpha. | |
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MedLine Citation:
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PMID: 19597757 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Postconditioning (PostC) has regenerated interest as a mechanical intervention against myocardial ischemia/reperfusion injury, but its molecular mechanisms remain elusive. This study tested the hypothesis that hypoxia inducible factor-1alpha (HIF-1alpha) plays a role in PostC-induced cardioprotection. Male Wistar rats were subjected to 30 min ischemia followed by 3 h of reperfusion (Control). PostC with 3 cycles of 10 s reperfusion and 10 s re-occlusion was applied at the onset of reperfusion. Relative to the Sham group, HIF-1alpha protein level was increased by 2.9-fold in the Control group, but its level was enhanced by 5.8-fold with PostC (P < 0.01 vs. Control). However, HIF-1alpha protein level was further augmented by 2.0-fold and 3.3-fold, respectively, when the prolyl hydroxylase inhibitor, dimethyloxalylglycine (DMOG, 40 mg/kg, i.p.) was given at 24 h before ischemia in both Control and PostC groups. PostC reduced infarct size by 24% compared with the Control (27 +/- 4.2% vs. 36 +/- 5.2%, P < 0.01), consistent with significant lower levels of plasma creatine kinase activity, index of cardiomyocyte apoptosis and caspase-3 activity. Although pretreatment with DMOG significantly reduced infarct size relative to the Control, the infarct-sparing effect of PostC was remarkably enhanced when DMOG was given before PostC (18 +/- 2.0% vs. 27 +/- 4.2% in PostC alone, P < 0.05). There was a significant linear inverse relationship between HIF-1alpha protein level and infarct size (r = -0.799, P < 0.01) among all groups. Furthermore, along with up-regulated HIF-1alpha expression, the levels of iNOS mRNA and protein were significantly increased in the PostC alone and DMOG plus PostC groups. In conclusion, these data suggest that HIF-1alpha is involved in cardioprotection by PostC and pharmacological augmentation of HIF-1alpha expression that enhances the infarct-sparing effect of PostC; iNOS, the downstream gene of HIF-1alpha, may participate in signaling pathways in mediating PostC's protection. |
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Authors:
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Huan-Xin Zhao; Xiao-Liang Wang; Ye-Hong Wang; Ye Wu; Xiao-Yu Li; Xiao-Ping Lv; Zhi-Qing Zhao; Rong-Rui Zhao; Hui-Rong Liu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-14 |
Journal Detail:
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Title: Basic research in cardiology Volume: 105 ISSN: 1435-1803 ISO Abbreviation: Basic Res. Cardiol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-09 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0360342 Medline TA: Basic Res Cardiol Country: Germany |
Other Details:
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Languages: eng Pagination: 109-18 Citation Subset: IM |
Affiliation:
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Department of Physiology, Shanxi Medical University, 56 South Xinjian Road, 030001, Taiyuan, Shanxi, People's Republic of China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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