Effects of estrogen on endothelial prostanoid production and cyclooxygenase-2 and heme oxygenase-1 expression

Abstract We studied the effects of 17β-estradiol (E 2 ) (10, 40 nM) on 2 vasoprotective pathways, i.e. cyclooxygenase-2 (COX-2)-dependent prostanoids and the antioxidant heme oxygenase-1 (HO-1), in human umbilical vein endothelial cells (HUVEC) exposed for 6 h to steady laminar shear stress (LSS, 10 dyn/cm 2 ), characteristic of atherosclerotic lesion-protected areas. COX-2 was induced by LSS versus static condition (SC). E 2 did not significantly affect COX-2 expression in HUVEC cultured in SC or exposed to LSS. Prostacyclin (PGI 2 ) and prostaglandin (PG)E 2 were induced while PGF 2α was reduced by LSS. E 2 caused no effect or a small reduction of prostanoid biosynthesis. In HUVEC cultured in SC or exposed to LSS, E 2 10 nM caused a comparable HO-1 induction (35–45%) while E 2 40 nM was 5-fold more potent in LSS-exposed HUVEC than in SC (290% and 58%, respectively). PGI 2 receptor antagonist RO3244794 did not affect HO-1 induction by E 2 . In conclusion, E 2 may restrain oxidant stress in the endothelium through HO-1 induction by a mechanism independent on PGI 2 signaling.