Conjugated Equine Estrogens Inhibit Progression of Atherosclerosis but Have No Effect on Intimal Hyperplasi or Arterial Remodeling Induced by Balloon Catheter Injury in Monkeys

Objectives. This study sought to determine the effects of estrogen treatment on atherosclerosis progression and the proliferative and structural 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 proliferation of smooth muscle cells. However, the effect of estrogen on the response of atherosclerotic arteries to transmural injury, as occurs in balloon catheter angioplasty in humans, is unknown. Methods. Forty-six ovariectomized cynomolgus monkeys were fed an atherogenic diet for 30 months; 25 received 175 μg/day of conjugated equine estrogens, and 21 served as untreated control animals. All animals underwent balloon catheter injury of the left iliac artery. Subsets of animals underwent necropsy study at 4, 7, 14 and 28 days after injury; injured and contralateral (uninjured) arteries were pressure-fixed and evaluated morphometrically. Results. Estrogen treatment resulted in 37% decrease (p < 0.05) in atherosclerosis (plaque area) in the uninjured artery. In response to injury, arterial cell proliferation increased at days 4 and 7, and intimal are was increased two- to threefold at day 28 (p < 0.05). Although estrogen treatment resulted in trend toward decreased arterial cell proliferation at day 4, there was evidence of increased cell proliferation in both medi and intim at day 7 (p < 0.05). However, there was no effect of estrogen treatment on intimal are or indexes of arterial remodeling in the injured artery at day 28 (p > 0.4). Conclusions. In contrast to previous studies of nonatherosclerotic animals, the results indicate that in the circumstance of transmural injury to arteries of primates with preexisting atherosclerosis, estrogen does not suppress arterial neointimal or structural responses to injury.