[Effect of estrogen replacement therapy in the early phase on atherosclerosis and PAI-1 in ovariectomized cholesterol-fed rabbit].

OBJECTIVE

To investigate the effect of estrogen replacement therapy (ERT) in the early phase on the atherosclerosis and the level of plasminogen activator inhibitor-1(PAI-1).

METHODS

Twenty-eight rabbits were randomly assigned to 4 groups: Group A, sham operation (n=7); Group B, ovariectomized without estradiol (n=7); Group C, ovariectomized with low-dose estradiol (n=7); and Group D, ovariectomized with high-dose estradiol (n=7). All rabbits were given 1% cholesterol diet for 12 weeks. Levels of blood lipid, estradiol, and PAI-1 were measured before the operation and at the end of the 4th and 12th weeks. Twelve weeks later, we took the aortas for pathological analysis and calculated the areas of atherosclerotic plaque.

RESULTS

After 12 weeks, the estradiol level of Group B was significantly lower than that of Group A, and that of Group D was obviously higher than Group A. There was no significant difference between Group C and A. The concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in Group B significantly increased compared with Group A (P<0.01). The levels of TC and LDL-C of Group C and D were significantly lower than those of Group A. Whereas the concentrations of triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) in Group B were lower than those of Groups A, C and D (P<0.01). In contrast to Groups A, C and D, the level of PAI-1 was significantly higher in the Group B (P<0.01), without significant differences among Groups A, C and D. The area of atherosclerotic lesion of aorta in Group B was significantly bigger than that of Group A, C and D. The areas of aortic atherosclerotic plaque in Group C and D were obviously smaller than those of Group A (P<0.01).

CONCLUSION

Transdermal estrogen replacement therapy in the early phase can improve the metabolism of the serum lipids, reduce the level of PAI-1, and probably provide the protective effect on the atheroma formation.