Key result
MMP-9 gene expression was 10-fold higher in male versus female rat aortic smooth muscle cells (p=0.003), and estradiol pretreatment in male rats reduced MMP-9 activity in aortic explants by 60% (p=0.03).
Why the study?
Do male and female rat aortic smooth muscle cells differ in MMP-9 production, and does estradiol treatment reduce MMP-9 activity?
Do male and female rat aortic smooth muscle cells differ in MMP-9 production, and does estradiol treatment reduce MMP-9 activity?
Answers are grounded in this paper and cite their sources.
Male rat aortic smooth muscle cells produce significantly more MMP-9 than female cells, and estradiol reduces MMP-9 activity in male rat aortic explants, suggesting a mechanism for the male predisposition to abdominal aortic aneurysms.
A predilection exists for men to develop abdominal aortic aneurysms (AAAs), but the reasons for this gender predisposition are not known. Matrix metalloproteinase-9 (MMP-9) has been implicated in both human and experimental AAAs. This investigation tested the hypothesis that male and female gender differences exist in the production of MMP-9 by rat aortic smooth muscle cells (RASMCs).In the first set of experiments, cultured male and female RASMCs were stimulated with interleukin-1 beta (IL-1beta) at 2 ng/mL. Messenger RNA was extracted from the RASMCs and gene expression of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1), an MMP-9 inhibitor, was measured by quantitative real-time polymerase chain reaction. Cell culture media were collected for measurement of MMP-9 protein levels and MMP-9 activity by Western blotting and gelatin zymography, respectively. In the second set of experiments, male RASMCs were treated with 17-beta-estradiol (10(-10) to 10(-6) mol/L) and MMP-9 activity was measured. In the third set of experiments, male rats were pretreated with estradiol, and MMP-9 activity was measured in the media from explanted aortas.MMP-9 gene expression was 10-fold higher in male versus female RASMCs (p=0.003). MMP-9 protein levels (p=0.005) and gelatinolytic activities (p=0.01) were also greater in male than female RASMCs. TIMP-1 expression was fourfold higher in male versus female RASMCs (p<0.001). Estradiol-treated male RASMCs did not exhibit a decrease in MMP-9 activity. But aortic explants from male rats pretreated with 17-beta-estradiol had 60% less MMP-9 activity than explants from male controls (p=0.03).MMP-9 and TIMP-1 are greater in male than in female RASMCs. These findings support the tenet that gender-related differences in MMP-9 may contribute to AAA formation.
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Woodrum et al. (2005) studied Abdominal aortic aneurysms. 17-beta-estradiol vs. Female RASMCs and male controls was evaluated on MMP-9 gene expression and activity (10-fold higher in males; 60% less with estradiol, p=0.003). MMP-9 gene expression was 10-fold higher in male versus female rat aortic smooth muscle cells (p=0.003), and estradiol pretreatment in male rats reduced MMP-9 activity in aortic explants by 60% (p=0.03).
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