Estrogen stimulation of COX-2-derived PGI2 confers atheroprotection.
Although selective cyclooxygenase-2 (COX-2) inhibitors provide relief from pain and inflammation, they also reduce the formation of the atheroprotective prostaglandin I2 (PGI2). They do not reduce the formation of the COX-1-derived thromboxane A2 (TXA2), however, which is both atherogenic and a potent vasoconstrictor. For this reason, the effects of TXA2 might be exacerbated during extended therapy with COX-2 inhibitors, potentially predisposing patients to heart attack and stroke. Recent studies have demonstrated that the atheroprotective effects of estrogen are induced through PGI2 production, through COX-2 activation. This explains how estrogen production in pre-menopausal females is beneficial for the heart and also raises the possibility that COX-2 inhibitors might be particularly hazardous to females.
Shah
Bukhtiar H
BH
Section on Hormonal Regulation, Endocrinology & Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, MD 20892-4510, USA. shahb@mail.nih.gov
D001161:Arteriosclerosis / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D004789:Enzyme Activation / Q000187:drug effects; D011464:Epoprostenol / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013268:Stimulation, Chemical
D004967:Estrogens; D008565:Membrane Proteins; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases