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Attenuation of myocardial injury by postconditioning: role of hypoxia inducible factor-1α

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Abstract

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-1α (HIF-1α) 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-1α 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-1α 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-1α protein level and infarct size (r = −0.799, P < 0.01) among all groups. Furthermore, along with up-regulated HIF-1α 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-1α is involved in cardioprotection by PostC and pharmacological augmentation of HIF-1α expression that enhances the infarct-sparing effect of PostC; iNOS, the downstream gene of HIF-1α, may participate in signaling pathways in mediating PostC’s protection.

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Acknowledgments

This work was supported in part by National Nature Scientific Foundation of People’s Republic of China (No.30572084 to Hui-Rong Liu, No.30700276 to Xiao-Liang Wang), and award of Technological Innovation of Taiyuan City (08122085 to Huan-Xin Zhao).

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Authors and Affiliations

  1. Department of Physiology, Shanxi Medical University, 56 South Xinjian Road, 030001, Taiyuan, Shanxi, People’s Republic of China

    Huan-Xin Zhao, Xiao-Liang Wang, Ye-Hong Wang, Ye Wu, Xiao-Yu Li, Xiao-Ping Lv, Rong-Rui Zhao & Hui-Rong Liu

  2. Key Laboratory of Cellular Physiology, Chinese Education Ministry, Shanxi Medical University, 030001, Taiyuan, People’s Republic of China

    Huan-Xin Zhao, Xiao-Liang Wang, Rong-Rui Zhao & Hui-Rong Liu

  3. Department of Biomedical Sciences, Mercer University School of Medicine, 4700 Waters Avenue, Savannah, GA, 31404-3089, USA

    Zhi-Qing Zhao

  4. School of Basic Medical Sciences and Cardiovascular Research Institute, Capital Medical University, 100069, Beijing, People’s Republic of China

    Hui-Rong Liu

  5. Shanxi College of Traditional Chinese Medicine, 030012, Taiyuan, China

    Huan-Xin Zhao

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  1. Huan-Xin Zhao
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Correspondence to Hui-Rong Liu.

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Zhao, HX., Wang, XL., Wang, YH. et al. Attenuation of myocardial injury by postconditioning: role of hypoxia inducible factor-1α. Basic Res Cardiol 105, 109–118 (2010). https://doi.org/10.1007/s00395-009-0044-0

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  • DOI: https://doi.org/10.1007/s00395-009-0044-0

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