Inhibitory effect of estrogen on Rac1-expression in monocytes.
Recruitment of circulating monocytes into the vasculature and release of reactive oxygen species (ROS) promote atherogenesis. Rac1-GTPase is an essential component of the superoxide-producing NADPH-oxidase complex. Estrogens inhibit production of vascular reactive oxygen species. Angiotensin II as well as overexpression of the constitutively active mutant RacL61 increased ROS production in monocytes. AngII-mediated ROS release was completely inhibited by overexpression of the dominant negative mutant RacN17 or treatment with 17beta-estradiol. 17beta-Estradiol reduced Rac1-expression concentration- and time-dependently and decreased basal, as well as AngII-induced Rac1 activity. The effects of 17beta-estradiol were receptor-mediated. In vivo, down-regulation of Rac1 by 17beta-estradiol was observed in human mononuclear cells of women with elevated 17beta-estradiol levels after controlled ovarian hyperstimulation. In summary, the data show that down-regulation of Rac1-GTPase contributes to the inhibition of angiotensin II-mediated superoxide release by 17beta-estradiol in monocytes.
Adam
Oliver
O
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, D-66421 Homburg/Saar, Germany. oliver.adam@uks.eu
Hagel
Marion
M
Theobald
Katharina
K
Böhm
Michael
M
Laufs
Ulrich
U
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*
D004967:Estrogens; D017382:Reactive Oxygen Species; D013481:Superoxides; D000804:Angiotensin II; D004958:Estradiol; D020830:rac1 GTP-Binding Protein