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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2116.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Gender Differences in Experimental Aortic Aneurysm Formation

Gorav Ailawadi; Jonathan L. Eliason; Karen J. Roelofs; Indranil Sinha; Kevin K. Hannawa; Eric P. Kaldjian; Guanyi Lu; Peter K. Henke; James C. Stanley; Stephen J. Weiss; Robert W. Thompson; Gilbert R. Upchurch, Jr

From Jobst Vascular Research Laboratories, Section of Vascular Surgery (G.A., J.L.E., K.J.R., I.S., K.K.H., P.K.H., J.C.S., G.R.U.), Section of Transplant Surgery (G.L.), Department of Pathology (E.P.K.), and Division of Molecular Medicine and Genetics, Department of Internal Medicine (S.J.W.), University of Michigan Medical School, Ann Arbor; and the Section of Vascular Surgery, Department of Surgery and Department of Cell Biology and Physiology (R.W.T.), Washington University Medical School, St Louis, Missouri.

Correspondence to Dr Gilbert R. Upchurch Jr, University of Michigan Medical Center, 2210 Taubman Health Care Center, 1500 E Medical Center Drive, Ann Arbor, MI 48109-0329. E-mail riversu{at}umich.edu

Objective— It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs).

Methods and Results— Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase.

Conclusions— These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.

Male rats demonstrated larger aortic dilatation than females after elastase exposure. Next, female rat aortas transplanted into males after elastase exposure lost aneurysm resistance. Finally, estradiol inhibited experimental aneurysm formation. Aneurysms correlated with increased macrophage and MMP-9 infiltration. Gender-related differences in aneurysms may be estrogen-mediated via reductions in macrophage MMP-9.

Key Words: aorta • aneurysm • genetic • estrogen • metalloproteinase

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