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Hearts From Rodents Exposed to Intermittent Hypoxia or Erythropoietin Are Protected Against Ischemia-Reperfusion Injury
Open accessAbstract
Background— Preconditioning phenomena provide evidence for adaptive responses to ischemia that have important implications for treatment/prevention of myocardial infarction. Hypoxia-inducible factor 1 (HIF-1) mediates adaptive transcriptional responses to hypoxia/ischemia. Methods and Results— Exposure of wild-type mice to intermittent hypoxia resulted in protection of isolated hearts against ischemia-reperfusion injury 24 hours later. Cardiac protection induced by intermittent hypoxia was lost in Hif1a +/ − mice heterozygous for a knockout allele at the locus encoding HIF-1α. Erythropoietin (EPO) mRNA expression was induced in kidneys of wild-type mice subjected to intermittent hypoxia, resulting in increased plasma EPO levels. EPO mRNA expression was not induced in Hif1a +/ − mice. EPO administration to rats increased functional recovery and decreased apoptosis in isolated hearts subjected to ischemia-reperfusion 24 hours later. Conclusions— Hearts isolated from rodents subjected to intermittent hypoxia or EPO administration are protected against postischemic injury. Cardiac protection induced by intermittent hypoxia is critically dependent on Hif1a gene dosage. Our data suggest that additional studies to evaluate therapeutic applications of EPO administration are warranted.
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Cites
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Self-citation
Cited by
Weidemann, A., & Johnson, R. S. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.12 · Cited by 941
Prabhakar, N. R., & Semenza, G. L. (2012) · Physiological Reviews · doi:10.1152/physrev.00030.2011 · Cited by 641
Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554
Chong, Z. Z., Li, F., & Maiese, K. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.02.004 · Cited by 536
Hypoxia. 2. Hypoxia regulates cellular metabolism
Wheaton, W. W., & Chandel, N. S. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00485.2010 · Cited by 426
Metadata
- Authors
- Cai, Z., Manalo, D. J., Wei, G., Rodriguez, E. R., Fox-Talbot, K., Lu, H., Zweier, J. L., & Semenza, G. L.
- Venue
- Circulation
- Published
- 2003-07-08
- Volume
- 108
- Issue
- 1
- Pages
- 79-85
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2129932871
- Cited by
- 557
- References
- 1
- FWCI
- 27.85
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Hearts From Rodents Exposed to Intermittent Hypoxia or Erythropoietin Are Protected Against Ischemia-Reperfusion Injury. https://app.cochat.ai/papers/10.1161/01.cir.0000078635.89229.8a
- The paper
- Cai, Z., Manalo, D. J., Wei, G., Rodriguez, E. R., Fox-Talbot, K., Lu, H., Zweier, J. L., & Semenza, G. L. (2003). Hearts From Rodents Exposed to Intermittent Hypoxia or Erythropoietin Are Protected Against Ischemia-Reperfusion Injury. Circulation. https://doi.org/10.1161/01.cir.0000078635.89229.8a
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