17 Beta-estradiol attenuates development of angiotensin II-induced aortic abdominal aneurysm in apolipoprotein E-deficient mice.
OBJECTIVE
Angiotensin II (Ang II) promotes vascular inflammation, accelerates atherosclerosis, and induces abdominal aortic aneurysm (AAA). These changes were associated with activation of nuclear factor (NF)-kappaB-mediated induction of proinflammatory genes. The incidence of AAA in this model was higher in male than in female mice, and the vascular effects of estrogen may be associated with anti-inflammatory actions. The present study was undertaken to test the hypothesis that estrogen can attenuate Ang II-induced AAA in apolipoprotein E-deficient mice via its anti-inflammatory mechanism.


RESULTS
Infusion of Ang II (1.44 mg/kg per d for 1 month) induced AAA in 90% of the animals (n=20) with an expansion of the suprarenal aorta (diameter 1.9+/-0.14 mm versus <1 mm in normal mice). In mice treated with 17beta-estradiol (E2, 0.25-mg subcutaneous pellets), Ang II induced AAA only in 42% of the animals (n=19) with a significant reduction of average diameters of the suprarenal aorta (1.5+/-0.14 mm). E2 also decreased the expressions of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, E-selectin, monocyte chemotactic protein-1, and macrophage-colony stimulating factor in the aorta.


CONCLUSIONS
These data suggest that attenuation of AAA by E2 is associated with inhibition of proinflammatory gene expression.
Martin-McNulty
Baby
B
Department of Pharmacology, Berlex Biosciences, Richmond, CA 94806, USA.
Tham
Doris M
DM
da Cunha
Valdeci
V
Ho
Jerrick J
JJ
Wilson
Dennis W
DW
Rutledge
John C
JC
Deng
Gary G
GG
Vergona
Ronald
R
Sullivan
Mark E
ME
Wang
Yi-Xin
YX
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency*; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008297:Male; D051379:Mice
D001057:Apolipoproteins E; D000804:Angiotensin II; D004958:Estradiol