title: Hypoxia-inducible factor-1α and vascular endothelial growth factor in the cardioprotective effects of intermittent hypoxia in rats.
abstract: OBJECTIVE
  This study investigated the effects of short-term intermittent hypoxia (IH) preconditioning on cardiac structure and function in rats and the influence of ischemia reperfusion (I/R) injury. Special attention was then paid to the involvement of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF).
  
  
  METHODS
  Wistar rats were given IH treatment for 1, 7, 14, or 28 days. Some of them were thereafter subject to myocardial infarction surgery. Right ventricle systolic pressure (RVSP), myocardial capillary density (CD), and mRNA/protein expression of HIF-1α, VEGF, and Bcl-2 in rat myocardial tissue were determined. Apoptotic cell number was determined by TUNEL staining, and concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured.
  
  
  RESULTS
  IH treatment for 1, 7, 14, and 28 days reduced the myocardial infarction size, whereas IH for 28 days increased the RVSP, ratio of right to left ventricle weight (RV/LV+S), and CD. IH up-regulated the mRNA and protein levels of HIF-1α, VEGF, and Bcl-2 both under normal and I/R conditions. The induced expression of HIF-1α and VEGF by IH reached a peak after 7 days of treatment. Moreover, IH for 28 days induced cardiomyocyte apoptosis, whereas prior treatment with IH for 1, 7, 14, and 28 days all markedly attenuated the apoptosis effected by the subsequent I/R injury. IH also decreased the concentrations of MDA but increased those of SOD in myocardial tissue of both in normal rats and following I/R.
  
  
  CONCLUSIONS
  The present study demonstrates that short-term IH protects the heart from I/R injury through inhibiting apoptosis and oxidative stress. The up-regulation of HIF-1α and VEGF by short-term IH may participate in the cardioprotective effect of IH.
authors: Department of Geriatrics, The First Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors: Zhang
authors: Z
authors: Wang
authors: Liang-Yi
authors: LY
authors: Si
mesh_terms: D000818:Animals; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control*; D017931:DNA Primers; D000860:Hypoxia / Q000517:prevention & control*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D017931:DNA Primers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D008315:Malondialdehyde