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

Prostaglandins Other Lipid Mediat. 2012 Aug;98(3-4):122-8. doi: 10.1016/j.prostaglandins.2012.01.006. Epub 2012 Feb 6.

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.

MeSH terms

  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Estrogens / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Heme Oxygenase-1 / metabolism*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / enzymology*
  • Humans
  • Prostaglandins / biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stress, Mechanical

Substances

  • Estrogens
  • Prostaglandins
  • RNA, Messenger
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Cyclooxygenase 2
  • PTGS2 protein, human