Effect of estrogen therapy on vascular perlecan and metalloproteinases 2 and 9 in castrated rats

AIM: To study the effects of estrogen therapy on the expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and perlecan in the vascular wall. METHODS: Twenty 180-day-old Wistar rats were castrated and treated 1 week later for a period of 4 weeks with one of the following: (1) placebo; (2) 0.5 μg/day estradiol benzoate (E(2)B); (3) 5 μg/day E(2)B; (4) 50 μg/day E(2)B. A fifth group consisted of rats that had not been castrated. Following treatment, expression of MMP-2 and MMP-9 mRNA (MMP-2(RNA) and MMP-9(RNA), respectively) was analyzed by real-time PCR, and expression of MMP-2 (MMP-2(IH)), MMP-9 (MMP-9(IH)) and perlecan was quantified by immunohistochemistry, in carotid walls. RESULTS: There were no differences among castrated groups for MMP-2(RNA) (p = 0.1969) and for MMP-9(RNA) (p = 0.1828); however, a correlation was observed between E(2)B dose and MMP-9(RNA) levels (r = 0.471, p = 0.018). Differences among groups were observed for MMP-2(IH), MMP-9(IH) and perlecan (p < 0.0001), wherein higher levels were observed in animals treated with estrogen therapy, correlating with E(2)B doses in the case of MMP-9 (r = 0.441, p = 0.026) and perlecan (r = 0.574, p = 0.005). CONCLUSIONS: Estrogen therapy correlates with higher levels of MMP-2, MMP-9 and perlecan in the extracellular matrix of carotid walls in castrated rats, in a dose-dependent manner. There was a dose-response effect of E(2)B on the expression of MMP-9 mRNA and, possibly, MMP-2 mRNA.