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ABSTRACT
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 (E2B); (3) 5 μg/day E2B; (4) 50 μg/day E2B. 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 E2B 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 E2B 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 E2B on the expression of MMP-9 mRNA and, possibly, MMP-2 mRNA.
Conflict of interest L. M. Pompei and C. E. Fernandes have received sponsorship from Bayer to attend international congresses. The other authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Source of funding This study was financed by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – process # 2009/11382-6).