[abstract] HYPERBARIC OXYGEN UPREGULATES VEGF THROUGH A HIF-1 PATHWAY

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[abstract] HYPERBARIC OXYGEN UPREGULATES VEGF THROUGH A HIF-1 PATHWAY

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Title: [abstract] HYPERBARIC OXYGEN UPREGULATES VEGF THROUGH A HIF-1 PATHWAY
Author: Murphy, PS; Hansen, BK; Khiabani, KT; Stephenson, LL; Wang, WZ; Zamboni, WA
Abstract: BACKGROUND: Hyperbaric oxygen (HBO) is known to have a protective effect on ischemia-reperfusion (IR) injury. Previous research has shown that HBO induces VEGF mRNA in ischemic tissue. HIF-1 is a well-described inducer of VEGF under hypoxic conditions, and we suspect that HIF-1 is also involved in the hyperoxic increase in VEGF mRNA. To evaluate this we have utilized YC-1, a documented HIF-1 blocker, to measure the effects of HBO on VEGF mRNA. MATERIALS AND METHODS: A gracilis flap was raised in 28 male Wistar rats, which were divided into four groups (n=7/group): (1) IR, (2) IR-HBO, and (3) IR-HBO + 30 microg/g of YC-1 suspended in 0.6 microl/g DMSO, and (4) IR-HBO + 0.6 microl/g DMSO alone. The injections were given intraperitoneally 24 hours prior to surgery. The flap was clamped to produce four hours of ischemia, with HBO treatment (100percent O2 at 2.5 ATA) given during the last 90 minutes. Following 30 minutes of reperfusion, 30mg tissue samples were taken from the reperfused gracilis flap and other nonischemic tissues, and immediately placed in RNAlater. RNA purification, reverse transcriptase, and PCR for VEGF mRNA were performed. The results are reported as percent GAPDH (reference gene), mean + SEM. ANOVA was used for group mean comparisons with a p less than 0.05 was accepted as significant. RESULTS: There was a significant increase in VEGF mRNA expression (82percent) in the gracilis muscle in IR+HBO compared to IR (10.54 +/- 1.95percent v. 5.79 +/- 0.87percent, p less than 0.01). The HIF-1 blocker, YC-1, blocked the HBO-induced increase in VEGF mRNA to a level similar to IR (6.96 +/- 2.77percent). This reduction was not seen in the DMSO (vehicle) group. CONCLUSIONS: These results show that HBO may exert its effect on VEGF-mRNA through a HIF-1-dependent pathway. By blocking HIF-1 with YC-1, the HBO-induced increase in VEGF mRNA was attenuated.
Description: Undersea and Hyperbaric Medical Society, Inc. (http://www.uhms.org )
URI: http://archive.rubicon-foundation.org/1696
Date: 2005

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  • UHMS Meeting Abstracts
    This is a collection of the published abstracts from the Undersea and Hyperbaric Medical Society (UHMS) annual meetings.

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