17β-Estradiol attenuates intimal hyperplasia and macrophage accumulation with a reduction in monocyte chemoattractant protein 1 expression in a vein graft model

Objective:Autogenous vein grafts are commonly used for arterial reconstructive procedures. Their success is limited by the development of intimal hyperplasia, a fibroproliferative disease that predisposes the grafts to occlusive stenosis. Our goal was to assess whether 17beta-estradiol (E-2) inhibits vein graft intimal hyperplasia coincident with a reduction in monocyte chemoattractant protein 1 (MCP-1) expression and macrophage accumulation. Method: Male Lewis rats were implanted with time-release pellets that contained 0.5 mg E-2 (E5 group) or placebo (PL group). Epigastric vein to common femoral artery interposition grafts were harvested at 2, 4, 8, and 12 weeks after surgery. We assessed macrophage/monocytes numbers, proliferating cell nuclear antigen, MCP-1, and transforming growth factor-PI with use of immunohistochemistry. MCP-1 message expression was quantified by real-time polymerase chain reaction. Results. The time-release pellets raised the serum E-2 level to greater than 250 pg/mL on the day of surgery. Serum E-2 level declined to 43 +/- 13 pg/mL by 4 weeks and to baseline by 6 weeks. We found that the neointimal area ratio was reduced significantly in the E5 group at 2 and 4 weeks (45%, P < .05, and 68%, P < 0.05, respectively) relative to that in the PL group. The number of proliferating cells was reduced in the E5 group. There was a significant attenuation of MCP-1 expression and of the number of macrophages accumulating in the graft with E2 treatment. Furthermore, MCP-1 messenger ribonucleic acid expression was also significantly attenuated in the E5 group at 4 weeks when compared to the PL group. There was no significant difference between the two groups in the expression of transforming growth factor-beta1. Conclusions: E-2 treatment reduces vein-graft intimal hyperplasia coincident with a reduction in MCP-1 expression, macrophage accumulation, and cell proliferation.