Effects of estradiol on circulating P-selectin.
The membrane protein P-selectin tethers leukocytes to endothelial cells (EC) and on activated platelets, and may play a role in atherosclerosis. Lower plasma levels of a soluble (c) P-selectin have recently been observed in premenopausal women compared to those in men. Given the antiatherogenic-cardioprotective effect of 17 beta-estradiol (E2), we hypothesized that E2 may down-regulate the expression of P-selectin and subsequently decrease cP-selectin levels. The effects of E2 on levels of plasma cP-selectin were evaluated during the menstrual cycle in healthy women (n = 18) and by measuring the effect of a single im injection of 10 mg E2 valerate (n = 9) or placebo (n = 10) on cP-selectin levels in healthy male volunteers. In women, the cyclic increase in serum E2 concentrations was accompanied by a decrease in cP-selectin levels from 110 ng/mL [95% confidence interval (CI), 100-137 ng/mL] in the follicular phase. The decrease reached a maximum of 13% (95% CI, 2-19%, P = 0.014) in the luteal phase. In men, cP-selectin decreased from a median of 139 ng/mL (95% CI, 113-165) to 125 ng/mL (95% CI, 97-152; P = 0.038) 4 days after E2 injection. The median baseline value of cP-selectin in the 19 male volunteers was 133 ng/mL (95% CI, 115-143 ng/mL) and was approximately 30% higher than those in the female volunteers during the midcycle (P = 0.024) and luteal (P = 0.012) phases, but was not different from that during the follicular phase. In sum, our study suggests that E2 lowers cP-selectin levels. An E2-induced decrease in cP-selectin reflects either decreased activation or damage of platelets and/or endothelial cells in vivo. Thus, our study may point to an additional mechanism for the residual antiatherogenic-cardioprotective effect of E2 that cannot be explained by its lipid-lowering effects.
Jilma
B
B
Department of Clinical Pharmacology, University of Vienna, Austria.
Hildebrandt
J
J
Kapiotis
S
S
Wagner
O F
OF
Kitzweger
E
E
Müllner
C
C
Monitzer
B
B
Krejcy
K
K
Eichler
H G
HG
D000328:Adult; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008597:Menstrual Cycle / Q000097:blood; D019007:P-Selectin / Q000097:blood* / Q000378:metabolism; D012727:Sex Characteristics; D012995:Solubility; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D019007:P-Selectin; D014841:von Willebrand Factor; D004958:Estradiol