Journal of Applied Physiology
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J Appl Physiol 92: 1064-1073, 2002. First published November 2, 2001; doi:10.1152/japplphysiol.00374.2001
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Vol. 92, Issue 3, 1064-1073, March 2002

Time- and dose-dependent differential upregulation of three genes by 17beta -estradiol in endothelial cells

Amparo C. Villablanca1, Kristine A. Lewis1, and John C. Rutledge2

1 Division of Cardiovascular Medicine and 2 Division of Endocrinology, Nutrition, and Vascular Medicine, University of California, Davis, California 95616-8636

The purpose of this study was to identify genetic targets in the vasculature for estrogen by profiling genes expressed in female human aortic endothelial cells exposed to various doses of 17beta -estradiol at differing concentrations and for differing periods of time. Our approach employed a RT-PCR-based cloning strategy of DNA differential display analysis, with differential expression verified by semiquantitative PCR performed with gene-specific primers. A significant increase in mRNA expression in response to 17beta -estradiol was observed for the following three genes: aldose reductase (3.4-fold), caspase homologue-alpha protein (4.2-fold), and plasminogen activator inhibitor-1 intron e (2.3-fold). For all three upregulated genes, estradiol-induced upregulation occurred with a similar time course and temporally clustered to the first 24 h after hormone treatment. In addition, the effect of estradiol dose on gene expression was consistent and occurred at physiological concentrations. Our results describe previously uncharacterized estradiol-sensitive time- and dose-dependent regulation of genes with potential importance to vascular function in human endothelial cells.

estrogen; estradiol; endothelial; cell culture; gene expression; differential display; vascular; RT-PCR; mRNA; aldose reductase; caspase homologue; plasminogen activator inhibitor-1


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