Gender Differences in Experimental Aortic Aneurysm Formation

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.

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

“…Male rats treated with 17b-estradiol had smaller aortic diameter, less macrophage infiltration, and elastin fragmentation as well as lower levels of MMP9 mRNA compared with the sham group. 64 The protective effects of estrogens were confirmed by other studies. 69,70 Additionally, Martin-McNultry et al 71 demonstrated that infusion of AngII induced AAA in 90% of Apoe À/À mice, whereas with 17b-estradiol treatment, only 42% of mice developed AAAs.…”

“…This apparent female protection was mediated by inhibitory effect of estradiol on the aortic wall macrophage infiltration and secretion of MMP9. 64 They also noticed that estrogen-related resistant phenotype was lost after transplantation of the female aorta into male rats. Moreover, the male and female aortas had nearly identical aortic structure before any intervention, suggesting a postinjury action of estrogen.…”

Differential Gender And Species Specific Formation of Aneurysms Using A Novel Method Of Inducing Abdominal Aortic Aneurysms

“…Protein concentrations were determined with BCA Protein Assay. Reverse Zymography was modified according to previous publications (3,4). Briefly, equal amounts of proteins (30 μg/lane) were loaded onto SDS-polyacrylamide gels (12%), which copolymerized with supernatant of smooth muscle cells and 1% gelatin.…”

Analysis of matrix metalloproteinase-9 gene polymorphism -1562 C/T in patients suffering from systemic sclerosis with and without ulcers

“…Male patients affected by type 1 diabetes mellitus have increased urinary MMP-9 (29). Gender difference in MMP-9 concentration was also shown in experimental aortic aneurysm (30) and rat aortic smooth muscle cells (31). Interestingly, other diseases may show gender differences in the MMP-9 -1562/TIMP-1 372 polymorphisms (32).…”