The atheroprotective effect of 17 beta-estradiol is not altered in P-selectin- or ICAM-1-deficient hypercholesterolemic mice.
The mechanisms that mediate the atheroprotective properties of estrogens remain obscure. In the present study, we evaluated the involvement of the adhesion molecule P-selectin, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in the atheroprotective effect of estrogens in murine models evaluating early steps of atherosclerosis. First, we studied the effect of 17 beta-estradiol (E2) administration for 12 weeks on fatty streak constitution at the root aorta of ovariectomized female mice deficient in apolipoprotein E (apoE) alone or deficient in both apoE and either P-selectin or ICAM-1. Compared with respective placebo groups, E2 significantly prevented the development of fatty streak, to a similar extent in all three genotypes (-70.0% in apoE(-/-), -77.4% in apoE(-/-) P-selectin(-/-), and -77.1% in apoE(-/-) ICAM-1(-/-)). Second, the endothelial expression of VCAM-1 at the root aorta was assessed by immunohistochemistry in either placebo or E2-treated ovariectomized C57BL/6 female mice fed an atherogenic diet. Compared with placebo, E2 treatment resulted in a 31.8% decrease of VCAM-1 endothelial expression at this lesion-prone site (P=0.03). These results demonstrate that P-selectin and ICAM-1 are not involved in the atheroprotective effect of estrogens, and suggest that VCAM-1 could play a role in this process.
Gourdy
P
P
INSERM U397, Institut Louis Bugnard, CHU Rangueil, 1 avenue Jean Poulhes, 31403 Toulouse Cedex 4, France. gourdyp@toulouse.inserm.fr
Mallat
Z
Z
Castano
C
C
Garmy-Susini
B
B
Mac Gregor
J L
JL
Tedgui
A
A
Arnal
J F
JF
Bayard
F
F
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*
D001057:Apolipoproteins E; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol