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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1627.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

17ß-Estradiol Attenuates Development of Angiotensin II–Induced Aortic Abdominal Aneurysm in Apolipoprotein E–Deficient Mice

Baby Martin-McNulty; Doris M. Tham; Valdeci da Cunha; Jerrick J. Ho; Dennis W. Wilson; John C. Rutledge; Gary G. Deng; Ronald Vergona; Mark E. Sullivan; Yi-Xin Wang

From the Department of Pharmacology (B.M.-M., V.d.C., J.H.J., R.V., M.E.S., Y.-X.W.) and Cardiovascular Research (G.C.D.), Berlex Biosciences, Richmond, and Department of Internal Medicine, School of Medicine (D.M.T., J.C.R.) and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine (D.W.W.), University of California at Davis, Calif.

Correspondence to Yi-Xin Wang, Department of Pharmacology, Berlex Biosciences, 2600 Hilltop Rd, PO Box 4099, Richmond, CA 94806. E-mail jim_wang{at}berlex.com

Objectives— 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)-B–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.

Methods and 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 17ß-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.

Key Words: estrogen • aneurysm • vascular inflammation • PPAR • gene expression

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