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

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2116-2122
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number11
DOIs
StatePublished - Nov 2004

Keywords

  • Aneurysm
  • Aorta
  • Estrogen
  • Genetic
  • Metalloproteinase

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