title: Effects of estrogen on endothelial prostanoid production and cyclooxygenase-2 and heme oxygenase-1 expression.
abstract: We studied the effects of 17β-estradiol (E₂) (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 6h to steady laminar shear stress (LSS, 10 dyn/cm²), characteristic of atherosclerotic lesion-protected areas. COX-2 was induced by LSS versus static condition (SC). E₂ did not significantly affect COX-2 expression in HUVEC cultured in SC or exposed to LSS. Prostacyclin (PGI₂) and prostaglandin (PG)E₂ were induced while PGF(2α) was reduced by LSS. E₂ caused no effect or a small reduction of prostanoid biosynthesis. In HUVEC cultured in SC or exposed to LSS, E₂ 10 nM caused a comparable HO-1 induction (35-45%) while E₂ 40 nM was 5-fold more potent in LSS-exposed HUVEC than in SC (290% and 58%, respectively). PGI₂ receptor antagonist RO3244794 did not affect HO-1 induction by E₂. In conclusion, E₂ may restrain oxidant stress in the endothelium through HO-1 induction by a mechanism independent on PGI₂ signaling.
authors.affiliation: Department of Medicine and Aging, "G. d'Annunzio" University, School of Medicine, 66100 Chieti, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcantoni
authors.forename: Luigia
authors.initials: L
authors.lastname: Di Francesco
authors.forename: Licia
authors.initials: L
authors.lastname: Totani
authors.forename: Antonio
authors.initials: A
authors.lastname: Piccoli
authors.forename: Virgilio
authors.initials: V
authors.lastname: Evangelista
authors.forename: Stefania
authors.initials: S
authors.lastname: Tacconelli
authors.forename: Paola
authors.initials: P
authors.lastname: Patrignani
mesh_terms: D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D004967:Estrogens; D011453:Prostaglandins; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human