Effects of acute and adaptive hypoxia on heat shock protein expression in hepatic tissue.

This experimental study was designed to analyze the expression of heat shock protein (HSP) in hepatic tissue induced by acute and adaptive hypoxic hypoxia. Rabbits were exposed to 5000 m simulated altitude at 11% O(2) in a chamber. Total antioxidant status (TAS) plasma content showed a significant decrease in the acute and adaptive hypoxia groups compared with the control group. Regarding TAS, there was no statistically significant difference between the acute and adaptive hypoxia groups. Histopathological evidence of liver injury was observed in study groups. Immunohistochemical analysis showed diffuse HSP70 staining in the hepatocytes in acute hypoxia group. Staining was focal and prominent in pericentral hepatocytes in the adaptive hypoxia group. As HSP expression appeared increased, total injury score increased as well. There was an inverse correlation between HSP and TAS, but it did not reach statistical value. Our results confirmed the expression of HSP in hepatic tissue related to defense against cellular injury in a hypoxia model. It is an early response in acute hypoxia and may decrease in adaptive hypoxia. It seems that HSP is induced, rather than protectively, as an early marker of liver injury. HSP70 induction and overexpression seem to be, at least in part, explained by impaired antioxidant defense mechanisms.

The effects of acute and intermittent hypoxia on the expressions of HIF-1α and VEGF in the left and right ventricles of the rabbit heart.

OBJECTIVE: Hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are involved in signaling mechanisms of cellular responses to hypoxia. These factors have been investigated in tissue samples by simulating different altitudes by changing the percentage of oxygen. We aimed first to evaluate the effect of normobaric, systemic hypoxia (11% O2) on HIF-1α and VEGF mRNA levels in the heart muscle; secondly, to compare the levels of HIF-1α and VEGF mRNA in the left and right ventricle muscles. METHODS: In this experimental study, 33 New Zealand male rabbits were assigned to control, acute hypoxia (4 hours) and intermittent hypoxia (4 hours/day for 14 days) groups (n=11/group). Total RNA was isolated from right and left ventricles of the heart. The expressions of HIF-1α and VEGF mRNAs were investigated by using Reverse Transcription Polymerase Chain Reaction (RT-PCR) method. The obtained data were compared by using ANOVA and paired t-test. RESULTS: The results indicated that left ventricle VEGF mRNA expressions in both acute and intermittent hypoxia groups (1.08 ± 0.15 and 1.03 ± 0.19, respectively) were higher than that in the control group (0.88 ± 0.15) (p=0.03). Hypoxia treatments did not significantly alter HIF-1α mRNA in both ventricles (p=0.60 and p=0.51 for left and right ventricles, respectively). CONCLUSION: Since systemic hypoxia results in induction of VEGF mRNA up-regulation only in left ventricle, it could be related to its higher metabolic activity and oxygen utilization. Hypoxia induced changes in the expression of HIF-1α mRNA may not be the only determining factor for HIF-1/VEGF pathway induction or the observed VEGF induction could be through other hypoxia sensitive pathways.