Hypoxic induction of adrenomedullin in cultured human umbilical vein endothelial cells

Objectives The current study evaluated the hypoxic induction of adrenomedul lin gene expression and secretion, and its mechanism in cultured human umbi lical 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 adrenom edullin expression in HUVEC, The transcriptional component of adrenomedulli n gene regulation was assessed by nuclear run-off experiments, and adrenome dullin mRNA half-life was measured by actinomycin D experiments. Results We found that hypoxic conditions (1-3% oxygen) significantly increa sed adrenomedullin mRNA and protein in HUVEC, This increase was inversely p roportional to oxygen tension and was reversible upon re-exposure to a 21% oxygen environment Nuclear run-off experiments revealed the enhanced transc riptional rate of adrenomedullin gene. Next, actinomycin D experiments reve aled the enhanced adrenomedullin mRNA stability, Conclusions These results indicate that hypoxia increases adrenomedullin ge ne expression and secretion in HUVEC by transcriptional and post-transcript ional mechanisms. Hypoxic induction of adrenomedullin may play a pathophysi ological role in the vascular systems.