title: Aldosterone increases osteopontin gene expression in rat endothelial cells.
abstract: Aldosterone is currently recognized as one of the important risk hormones for cardiovascular disease. However, the cellular mechanism by which aldosterone affects the process of cardiovascular injury has not been well understood. In the present study, we investigated whether aldosterone induces pro-inflammatory genes expression in rat aortic endothelial cells. Aldosterone significantly increased steady-state osteopontin mRNA and protein levels, but not those of adhesion molecules or chemokine. The stimulatory effect of aldosterone on osteopontin expression was time-dependent (3-24h) and dose-dependent (10(-10)-10(-6)M), and abolished by a mineralocorticoid receptor (MR) antagonist spironolactone, but not by a glucocorticoid receptor antagonist RU486. The aldosterone-induced osteopontin mRNA expression was completely blocked by a transcription inhibitor, actinomycin D, and a protein synthesis inhibitor, cycloheximide. Thus, the present study demonstrated for the first time that aldosterone directly acts on endothelial cells to induce osteopontin gene expression via MR-mediated genomic action, which may be responsible for the initiation of inflammation and fibrosis in cardiovascular tissue induced by aldosterone.
authors.affiliation: Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirono
authors.forename: Noriko
authors.initials: N
authors.lastname: Suzuki
authors.forename: Maya
authors.initials: M
authors.lastname: Sakurada
authors.forename: Kyoichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Isao
authors.initials: I
authors.lastname: Minami
authors.forename: Fumiko
authors.initials: F
authors.lastname: Iwashima
authors.forename: Haruna
authors.initials: H
authors.lastname: Sakai
authors.forename: Toru
authors.initials: T
authors.lastname: Tateno
authors.forename: Ryuji
authors.initials: R
authors.lastname: Sato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists; D053495:Osteopontin; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D000451:Mineralocorticoid Receptor Antagonists; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D013148:Spironolactone; D015735:Mifepristone; D000450:Aldosterone; D003513:Cycloheximide