Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity.

Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-{alpha}.

Estradiol (E(2)) acts on the endothelium to promote vasodilatation through the release of several compounds, including prostanoids, which are products of arachidonic acid metabolism. Among these, prostacyclin (PGI2) and thromboxane A2 (TXA2) exert opposite effects on vascular tone. The role of different estrogen receptors (ERs) in the PGI2/TXA2 balance, however, has not been fully elucidated.

Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.

Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.

Therapeutic dosages of oral or transdermal estradiol did not modify sCD40L levels in postmenopausal women.

The CD40/CD40L system is considered a crucial modulator of the inflammatory process underlying the progression and complication of atheroma plaques. The soluble fraction of CD40L (sCD40L) is a reliable indicator of the CD40/CD40L system. Our purpose was to investigate whether a therapeutic dose of estradiol, by either the oral or the transdermal route, was associated with changes in circulating levels of sCD40L.

Transdermal estradiol reduces F2alpha-isoprostane levels in postmenopausal women.

Objective: F2alpha-isoprostanes are considered the most reliable index of in vivo oxidative stress. Given the implication of oxidative stress in the pathogenesis of atherosclerosis, we investigated the effects of hormone therapy on the plasma levels of F2alpha-isoprostanes.

Design: Sixty-one healthy postmenopausal women were treated in a randomized trial with estradiol either orally (2 mg/day, 28 women) or transdermally (50 mug/day, 33 women) for 4 weeks.

Raloxifene increases proliferation of human endothelial cells in association with increased gene expression of cyclins A and B1.

Objective: To examine the proliferative effect of of raloxifene on human umbilical-vein endothelial cells (HUVECs), and to investigate whether there is an associated increased expression of some key regulators of the cell cycle.

Design: Cell culture for different incubation times.

Setting: University research laboratory.

Estradiol counteracts oxidized LDL-induced asymmetric dimethylarginine production by cultured human endothelial cells.

Objective: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, is a novel cardiovascular risk factor produced by endothelial cells. ADMA levels are mainly regulated by the activity of dimethylarginine dimethylaminohydrolases (DDAH). Endothelial release of ADMA is increased in the presence of oxidized LDL cholesterol (oxLDL), whereas estrogens stimulate NO production by endothelial cells by increasing both expression and activity of NO synthase and by reducing ADMA levels.

Therapeutic dosages of raloxifene do not modify myeloperoxidase and F2alpha-isoprostane levels in postmenopausal women.

We investigated the effect of a therapeutic dose of raloxifene on the plasma levels of myeloperoxidase and F2alpha-isoprostanes, two markers of oxidative stress recently described as reliable indicators of coronary heart disease. Contrary to changes described in the literature for estrogens (E), raloxifene did not modify the levels of either myeloproxidase or F2alpha-isoprostanes after 3 or 6 months of treatment.

Effects of phytoestrogens genistein and daidzein on prostacyclin production by human endothelial cells.

The molecular mechanisms of the vascular effects of phytoestrogens are poorly studied. Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase (COX) in endothelium. This study examine the effects of two phytoestrogens, the isoflavones genistein and daidzein, on prostacyclin production by cultured human umbilical vein endothelial cells (HUVECs) and the possible role of not only estrogen receptors but also both COX isoforms.

Raloxifene promotes prostacyclin release in human endothelial cells through a mechanism that involves cyclooxygenase-1 and -2.

Objective: To examine the effects of raloxifene on prostacyclin production by human umbilical vein endothelial cells (HUVEC) and to shed light on the molecular details of that action.

Design: Cell culture for 4, 8, 16, 24, and 48 hours.

Setting: University research laboratory.

Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.

Objective: Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2.

Design: Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months.