Publication Date:
2004-11-20
Description:
Female gender affords relative protection from cardiovascular disease until the menopause. We report that estrogen acts on estrogen receptor subtype alpha to up-regulate the production of atheroprotective prostacyclin, PGI2, by activation of cyclooxygenase 2 (COX-2). This mechanism restrained both oxidant stress and platelet activation that contribute to atherogenesis in female mice. Deletion of the PGI2 receptor removed the atheroprotective effect of estrogen in ovariectomized female mice. This suggests that chronic treatment of patients with selective inhibitors of COX-2 could undermine protection from cardiovascular disease in premenopausal females.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Egan, Karine M -- Lawson, John A -- Fries, Susanne -- Koller, Beverley -- Rader, Daniel J -- Smyth, Emer M -- Fitzgerald, Garret A -- HL62250/HL/NHLBI NIH HHS/ -- HL70128/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Dec 10;306(5703):1954-7. Epub 2004 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15550624" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antioxidants/metabolism
;
Arteriosclerosis/metabolism/pathology/*prevention & control
;
Cardiovascular Diseases/chemically induced
;
Cells, Cultured
;
Cyclooxygenase 2
;
Cyclooxygenase 2 Inhibitors
;
Cyclooxygenase Inhibitors/adverse effects/pharmacology
;
Epoprostenol/biosynthesis/metabolism/*physiology
;
Estradiol/pharmacology
;
Estrogen Receptor alpha/metabolism
;
Female
;
Hydrogen Peroxide/pharmacology
;
Isoenzymes/*metabolism
;
Lactones/adverse effects/pharmacology
;
Lipid Peroxidation
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Muscle, Smooth, Vascular/drug effects/metabolism
;
Myocytes, Smooth Muscle/cytology/drug effects/metabolism
;
Ovariectomy
;
Oxidative Stress
;
Platelet Activation
;
Prostaglandin-Endoperoxide Synthases/*metabolism
;
Receptors, Epoprostenol/genetics/physiology
;
Receptors, LDL/genetics/physiology
;
Sex Characteristics
;
Sulfones/adverse effects/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
