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Hypoxic induction of adrenomedullin in cultured human umbilical vein endothelial cells

2001; Lippincott Williams & Wilkins; Volume: 19; Issue: Supplement Linguagem: Inglês

10.1097/00004872-200103001-00013

1473-5598

Teruhiko Ogita, Etsuo Hashimoto, Masao Yamasaki, Takashi Nakaoka, Rumiko Matsuoka, Yuji Kira, Toshiro Fujita,

Proteoglycans and glycosaminoglycans research

Objectives The current study evaluated the hypoxic induction of adrenomedullin gene expression and secretion, and its mechanism in cultured human umbilical vein endothelial cells (HUVEC). Methods HUVEC were exposed to hypoxia or normoxia as controls for 1 to 24 h. Using Northern blot analysis and a radioimmunoassay, we evaluated adrenomedullin expression in HUVEC. The transcriptional component of adrenomedullin gene regulation was assessed by nuclear run-off experiments, and adrenomedullin mRNA half-life was measured by actinomycin D experiments. Results We found that hypoxic conditions (1–3% oxygen) significantly increased adrenomedullin mRNA and protein in HUVEC. This increase was inversely proportional to oxygen tension and was reversible upon re-exposure to a 21% oxygen environment. Nuclear run-off experiments revealed the enhanced transcriptional rate of adrenomedullin gene. Next, actinomycin D experiments revealed the enhanced adrenomedullin mRNA stability. Conclusions These results indicate that hypoxia increases adrenomedullin gene expression and secretion in HUVEC by transcriptional and post-transcriptional mechanisms. Hypoxic induction of adrenomedullin may play a pathophysiological role in the vascular systems.