CONJUGATED EQUINE ESTROGENS INHIBIT PROGRESSION OF ATHEROSCLEROSIS BUT HAVE NO EFFECT ON INTIMAL HYPERPLASIA OR ARTERIAL REMODELING INDUCEDBY BALLOON CATHETER INJURY IN MONKEYS

Objectives. This study sought to determine the effects of estrogen tre atment on atherosclerosis progression and the proliferative and struct ural responses of the atherosclerotic arteries to injury. Background. Estrogen treatment suppresses the intimal response to arterial injury in nonatherosclerotic rodents and rabbits and inhibits the in vitro pr oliferation of smooth muscle cells. However, the effect of estrogen on the response of atherosclerotic arteries to transmural injury, as occ urs in balloon catheter angioplasty in humans, is unknown. Methods. Fo rty-six ovariectomized cynomolgus monkeys were fed an atherogenic diet for 30 months; 25 received 175 mu g/day of conjugated equine estrogen s, and 21 served as untreated control animals. All animals underwent b alloon catheter injury of the left iliac artery, Subsets of animals un derwent a necropsy study at 4, 7, 14 and 28 days after injury; injured and contralateral (uninjured) arteries were pressure-fixed and evalua ted morphometrically. Results. Estrogen treatment resulted in a 37% de crease (p < 0.05) in atherosclerosis (plaque area) in the uninjured ar tery. In response to injury, arterial cell proliferation increased at days I and 7, and intimal area was increased two- to threefold at day 28 (p < 0.05). Although estrogen treatment resulted in a trend toward decreased arterial cell proliferation at day 4, there was evidence of increased cell proliferation in both media and intima at day 7 (p < 0. 05). However, there was no effect of estrogen treatment on intimal are a or indexes of arterial remodeling in the injured artery at day 28 (p > 0.4). Conclusions. In contrast to previous studies of nonatheroscle rotic animals, the results indicate that in the circumstance of transm ural injury to arteries of primates with preexisting atherosclerosis, estrogen does not suppress arterial neointimal or structural responses to injury. (C)1998 by the American College of Cardiology.