title: Transcriptome analysis of aldosterone-regulated genes in human vascular endothelial cell lines stably expressing mineralocorticoid receptor.
abstract: A series of studies have demonstrated that endothelial cell is one of the target tissues of aldosterone. Here, we have conducted a transcriptome analysis of aldosterone-inducible genes in human endothelial cell lines stably expressing human mineralocorticoid receptor (MR) by retroviral system (MR-EAhy). We found that aldosterone in physiologic concentrations robustly induced MR-dependent transcriptional response in MR-EAhy. By DNA microarray analysis, we validated 12 aldosterone-up-regulated genes among which at least seven were concomitantly associated with increased protein expression. We also found five aldosterone-down-regulated genes. Among 11 aldosterone-up-regulated genes tested, mRNA expressions of three (ESM1, SNF1LK, ANGPTL4) were significantly up-regulated in aortic tissue from aldosterone-induced hypertensive rats compared to those from control rats, suggesting their potential pathophysiologic significance in vivo. In conclusion, using MR stably expressed human endothelial cell lines, we identified a variety of aldosterone-inducible genes, suggesting their possible roles in the development and/or the protection for aldosterone-induced vascular injury.
authors.affiliation: Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sekizawa
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Eri
authors.initials: E
authors.lastname: Hayakawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Suzuki
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000450:Aldosterone / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D005796:Genes; D017930:Genes, Reporter; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D049409:Luciferases, Firefly