Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta.
BACKGROUND
The atheroprotective effect of 17beta-estradiol (E(2)) has been suggested in women and clearly demonstrated in animals through both an effect on lipid metabolism and a direct effect on the cells of the arterial wall. It has been shown, for example, that E(2) promotes endothelium-dependent relaxation and accelerates reendothelialization in rats. Similar studies have been undertaken in mice to appreciate the molecular mechanism of this process.


RESULTS
We report here a model of electric carotid injury adapted from that described by Carmeliet et al (1997) that allows us to precisely evaluate the reendothelialization process. We demonstrate that E(2) accelerates endothelial regeneration in castrated female wild-type mice. In ovariectomized transgenic mice in which either the estrogen receptor (ER)-alpha or ERbeta gene has been disrupted, E(2) accelerated reendothelialization in female ERbeta knockout mice, whereas this effect was abolished in female ERalpha knockout mice.


CONCLUSIONS
This study demonstrates that ERalpha but not ERbeta mediates the beneficial effect of E(2) on reendothelialization and potentially the prevention of atherosclerosis.
Brouchet
L
L
INSERM U397, Institut L. Bugnard, CHU Rangueil, Toulouse, France.
Krust
A
A
Dupont
S
S
Chambon
P
P
Bayard
F
F
Arnal
J F
JF
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D020212:Carotid Artery Injuries / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002369:Castration; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005070:Evans Blue; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D011960:Receptors, Estrogen / Q000172:deficiency / Q000187:drug effects*; D012038:Regeneration; D013194:Staining and Labeling; D013997:Time Factors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D005070:Evans Blue; D004958:Estradiol