Role of hypoxia-inducible factor in cell survival during myocardial ischemia-reperfusion

Cell Death Differ. 2008 Apr;15(4):686-90. doi: 10.1038/cdd.2008.13. Epub 2008 Feb 8.

Abstract

Hypoxia-inducible factor (HIF) is the principal transcription factor involved in the regulation of transcriptional responses to hypoxia. During hypoxia, HIF-alpha levels accumulate and trigger an increase in expression of genes involved in glycolysis, glucose metabolism, mitochondrial function, cell survival, apoptosis, and resistance to oxidative stress. In this regard, HIF activation plays an essential role in triggering cellular protection and metabolic alterations from the consequences of oxygen deprivation. This suggests that HIF activation should confer protection against ischemia-reperfusion (I/R) injury, although this protection might require HIF activation before the onset of lethal ischemia. Studies using enhanced expression of HIF-1alpha suggest that its upregulation may be a beneficial therapeutic modality in the treatment or prevention of ischemic injury. HIF-regulated gene expression may mediate the late phase of preconditioning, and constitutive HIF activity may influence the expression of genes that are required for the cell to be able to respond to acute preconditioning. This article reviews the current literature on the role of HIF in balancing protection and cell death in the face of ischemia and I/R injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Hypoxia
  • Cell Survival
  • Enzyme Induction
  • Gene Expression Regulation
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ischemic Preconditioning, Myocardial
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control
  • Myocardium / enzymology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Nitric Oxide Synthase Type II / biosynthesis
  • Signal Transduction* / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1