17 beta-estradiol, but not raloxifene, decreases thrombomodulin in the antithrombotic protein C pathway

Citation
Ma. Richardson et al., 17 beta-estradiol, but not raloxifene, decreases thrombomodulin in the antithrombotic protein C pathway, ENDOCRINOL, 141(10), 2000, pp. 3908-3911
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
ENDOCRINOLOGY
ISSN journal
0013-7227 → ACNP
Volume
141
Issue
10
Year of publication
2000
Pages
3908 - 3911
Database
ISI
SICI code
0013-7227(200010)141:10<3908:1BBNRD>2.0.ZU;2-F
Abstract
Raloxifene is a nonsteroidal selective estrogen receptor modulator (SERM) t hat mimics the effects of estrogen on some plasma lipids and may have direc t effects on the vascular wall. The objective of this study was to determin e the effects of 17 beta-estradiol, raloxifene, and LY139,478 (a related be nzothiophene SERM) on the anticoagulant protein C pathway. In human vascula r endothelial cells activated with interleukin-1 (IL-1), we demonstrated de creased thrombomodulin-dependent protein C activation. 17 beta-estradiol re duced the anticoagulant properties of both unstimulated and IL-1-activated endothelial cells by decreasing thrombomodulin expression. In contrast, ral oxifene and LY139,478 enhanced the anticoagulant properties of both unstimu lated and IL-1-activated endothelial cells through upregulation of thrombom odulin. Regulation of the protein C pathway via thrombomodulin on vascular endothelium may be a novel mechanism by which SERMs could potentially confe r cardioprotective effects and reduce the thrombotic risk associated with H RT in compromised patients.