ANTIATHEROGENIC EFFECT OF ESTROGEN ABOLISHED BY BALLOON CATHETER INJURY IN CHOLESTEROL-CLAMPED RABBITS

The purpose of this study was to investigate the importance of an inta ct endothelial cell layer for the direct antiatherogenic effect of est rogen on the arterial wall. Thirty rabbits were bilaterally ovariectom ized and subjected to mechanical injury of the endothelium by balloon catheterization of the upper thoracic aorta. Immediately after the ope ration, treatment was initiated with either 17 beta-estradiol or place bo given intramuscularly. All rabbits were clamped at a similar plasma cholesterol level from 1 week before the operation until the experime nt was terminated 13 weeks later. In the undamaged aorta, ie, the aort ic arch, the lower thoracic aorta, and the upper abdominal aorta, the estrogen-treated rabbits had one third (P=.06), one sixth (P=.002), an d one seventh (P=.001), respectively, the accumulation of cholesterol of the placebo-treated rabbits. In the upper thoracic aorta that had b een subjected to mechanical injury of the endothelium, however, aortic cholesterol accumulation was not significantly different between the two groups. Similar results were obtained by histological evaluation o f the aortic tissues. Immunohistochemical staining with antibodies aga inst macrophages, smooth muscle cells, and T lymphocytes revealed no s ignificant differences in the intimal distribution of cells between es trogen-and placebo-treated rabbits, except for a higher number of T ly mphocytes per unit intimal area of the undamaged aortic arch (P<.0005) in the estrogen-treated-rabbits than the placebo-treated rabbits. Thi s is the first study to demonstrate that the antiatherogenic effect of estrogen is abolished by balloon catheter injury in cholesterol-clamp ed rabbits. These results may indicate that an intact endothelial cell layer is crucial for the direct antiatherogenic effect of estrogen on the arterial wall.