期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 24, 期 11, 页码 2116-2122出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000143386.26399.84
关键词
aorta; aneurysm; genetic; estrogen; metalloproteinase
资金
- NHLBI NIH HHS [T32-HL07853-05, K08 HL67885-01] Funding Source: Medline
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.
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