HIF‑1α may provide only short‑term protection against ischemia‑reperfusion injury in Sprague‑Dawley myocardial cultures

Wang,Siyang; Shao,Xin; Li,Xiaoxue; Su,Xiaojuan; Huo,Yongxu; Yang,Chunlei

doi:10.3892/mco.2016.764

HIF‑1α may provide only short‑term protection against ischemia‑reperfusion injury in Sprague‑Dawley myocardial cultures

Authors:
- Siyang Wang
- Xin Shao
- Xiaoxue Li
- Xiaojuan Su
- Yongxu Huo
- Chunlei Yang
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Affiliations: Department of Life Sciences, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: February 3, 2016 https://doi.org/10.3892/mco.2016.764
Pages: 579-583

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Abstract

Hypoxia‑inducible factor‑1 (HIF‑1α) exerts an important role in protecting against cardiac tissue damage, for example, following ischemia‑reperfusion (I/R), although the time frame during which it acts has yet to be fully elucidated. In the present study, a culture model of myocardial cells from Sprague‑Dawley rats was used to examine the expression levels of HIF‑1α and various downstream effectors at different times following I/R. The levels of HIF‑1α were manipulated by overexpressing HIF‑1α prior to I/R. HIF‑1α levels peaked at 6 h following I/R, subsequently decreasing to low levels. The levels of downstream effectors peaked at 48 h, and decreased almost to pre‑I/R levels by 72 h. These results suggest that HIF‑1α and its downstream targets offer only short‑term protection following I/R. These results may have implications for the treatment of I/R‑associated injury in a variety of clinical contexts.

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1	Eltzschig HK and Collard CD: Vascular ischaemia and reperfusion injury. Br Med Bull. 70:71–86. 2004. View Article : Google Scholar : PubMed/NCBI
2	Ockaili R, Natarajan R, Salloum F, Fisher BJ, Jones D, Fowler AA III and Kukreja RC: HIF-1 activation attenuates postischemic myocardial injury: Role for heme oxygenase-1 in modulating microvascular chemokine generation. Am J Physiol Heart Circ Physiol. 289:H542–H548. 2005. View Article : Google Scholar : PubMed/NCBI
3	Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, et al: C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell. 107:43–54. 2001. View Article : Google Scholar : PubMed/NCBI
4	Hofer T, Wenger R and Gassmann M: Oxygen sensing, HIF-1alpha stabilization and potential therapeutic strategies. Pflugers Arch. 443:503–507. 2002. View Article : Google Scholar : PubMed/NCBI
5	Stroka DM, Burkhardt T, Desbaillets I, Wenger RH, Neil DA, Bauer C, Gassmann M and Candinas D: HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia. FASEB J. 15:2445–2453. 2001.PubMed/NCBI
6	Lipsky PE, Brooks P, Crofford LJ, DuBois R, Graham D, Simon LS, van de Putte LB and Abramson SB: Unresolved issues in the role of cyclooxygenase-2 in normal physiologic processes and disease. Arch Intern Med. 160:913–920. 2000. View Article : Google Scholar : PubMed/NCBI
7	Harris AL: Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–47. 2002. View Article : Google Scholar : PubMed/NCBI
8	Bolli R, Shinmura K, Tang XL, Kodani E, Xuan YT, Guo Y and Dawn B: Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning. Cardiovasc Res. 55:506–519. 2002. View Article : Google Scholar : PubMed/NCBI
9	Murry CE, Jennings RB and Reimer KA: Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation. 74:1124–1136. 1986. View Article : Google Scholar : PubMed/NCBI
10	Adams JM, Difazio LT, Rolandelli RH, Luján JJ, Haskó G, Csóka B, Selmeczy Z and Németh ZH: HIF-1: A key mediator in hypoxia. Acta Physiol Hung. 96:19–28. 2009. View Article : Google Scholar : PubMed/NCBI
11	Ramírez-Bergeron DL, Runge A, Adelman DM, Gohil M and Simon MC: HIF-dependent hematopoietic factors regulate the development of the embryonic vasculature. Dev Cell. 11:81–92. 2006. View Article : Google Scholar : PubMed/NCBI
12	Date T, Belanger AJ, Mochizuki S, Sullivan JA, Liu LX, Scaria A, Cheng SH, Gregory RJ and Jiang C: Adenovirus-mediated expression of p35 prevents hypoxia/reoxygenation injury by reducing reactive oxygen species and caspase activity. Cardiovasc Res. 55:309–319. 2002. View Article : Google Scholar : PubMed/NCBI
13	Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N and Walsh K: Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 11:1096–1103. 2005. View Article : Google Scholar : PubMed/NCBI