Understanding the oestrogen action in experimental and clinical atherosclerosis.
Whereas hormone replacement/menopause therapy (HRT) in postmenopausal women increases the coronary artery risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of oestradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits in vivo a proinflammation at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. Endothelium is another important target for E2, as it potentiates endothelial NO and prostacyclin production, thus promoting the beneficial effects as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appears to be involved in the atheroprotective effect of E2. E2 also accelerates endothelial regrowth, thus favouring vascular healing. Finally, most of these effects of E2 are mediated by oestrogen receptor alpha, and are independent of oestrogen receptor beta. In summary, a better understanding of the mechanisms of oestrogen action not only on the normal and atheromatous arteries, but also on innate and adaptive immune responses is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective oestrogen receptor modulators.
Arnal
J F
JF
INSERM U589, IFR 31, CHU Toulouse-Rangueil, BP 84225, 31432 Toulouse Cedex 4, France. arnal@toulouse.inserm.fr
Douin-Echinard
V
V
Brouchet
L
L
Tremollières
F
F
Laurell
H
H
Lenfant
F
F
Gadeau
A P
AP
Guery
J C
JC
Gourdy
P
P
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000517:prevention & control; D001808:Blood Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D004958:Estradiol / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000502:physiology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced; D023421:Models, Animal
D047628:Estrogen Receptor alpha; D004958:Estradiol