von Hippel Lindau tumor suppressor and HIF-1 alpha : new targets of NSAIDs inhibition of hypoxia-induced angiogenesis

Nonsteroidal anti-inflammatory drugs (NSAIDs, inhibitors of cyclooxygenase enzymes that synthesize prostaglandins) inhibit angiogenesis essential for tissue repair and colon cancer growth. The mechanisms of NSAIDs inhibition of angiogenesis remain unexplained. Since hypoxia is a major stimulus for a...

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Bibliographic Details
Published in:The FASEB journal 2002-02, Vol.16 (2), p.264-266
Main Authors: Jones, Michael K, Szabo, Imre L, Kawanaka, Hirofumi, Husain, Syeda S, Tarnawski, Andrzej S
Format: Article
Language:English
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Summary:Nonsteroidal anti-inflammatory drugs (NSAIDs, inhibitors of cyclooxygenase enzymes that synthesize prostaglandins) inhibit angiogenesis essential for tissue repair and colon cancer growth. The mechanisms of NSAIDs inhibition of angiogenesis remain unexplained. Since hypoxia is a major stimulus for angiogenesis, the aim of this study was to determine the molecular mechanism(s) of NSAIDs inhibition of hypoxia-induced angiogenesis in gastric microvascular endothelial cells (RGMEC). We studied whether NSAIDs affect expression levels of the hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha ) and/or the von Hippel Lindau tumor suppressor (VHL). The rationale for this study is that HIF-1 alpha and VHL control hypoxia-induced expression of VEGF (the most potent angiogenic factor) and its specific receptor, Flt-1, major mediators of hypoxia-induced angiogenesis.
ISSN:0892-6638
DOI:10.1096/fj.01-0589fje