Upregulation of glutathione peroxidase offsets stretch-induced proatherogenic gene expression in human endothelial cells.

Objective: Localization of atherosclerotic plaques typically correlates with areas of biomechanical strain where shear stress is decreased while stretch, thought to promote atherogenesis through enhanced oxidative stress, is increased.

Methods And Results: In human cultured endothelial cells, nitric oxide synthase expression was exclusively shear stress-dependent whereas expression of glutathione peroxidase-1 (GPx-1), but not that of Cu(2+)/Zn(2+)-superoxide dismutase or Mn(2+)-superoxide dismutase, was upregulated solely in response to cyclic stretch. GPx-1 expression was also enhanced in isolated mouse arteries perfused at high pressure.

Certain progestins prevent the enhancing effect of 17beta-estradiol on NO-mediated inhibition of platelet aggregation by endothelial cells.

Objective: Estro-progestin treatments have been associated with an increased risk of thromboembolic events in postmenopausal women. This study examined whether progestins affect the stimulatory effect of estrogens on the endothelial formation of nitric oxide (NO), a potent antithrombotic factor.

Methods And Results: Experiments were performed with human endothelial cells.

Progestins overcome inhibition of platelet aggregation by endothelial cells by down-regulating endothelial NO synthase via glucocorticoid receptors.

Hormone replacement therapy with estroprogestin preparations is associated with an increased risk of venous and arterial thromboembolic events in postmenopausal women. This study examined whether progestins affect the formation of NO in endothelial cells, and, if so, to determine the underlying mechanism. Experiments were performed with human umbilical vein endothelial cells.