ABSTRACT
Estrogen inhibits the intimal proliferative response to arterial injury in nonatherosclerotic rodents and rabbits and inhibits the in vitro proliferation of smooth muscle cells. In contrast, although longterm estrogen treatment inhibits progression of diet-induced atherosclerosis, it had no effect on short-term (28 day) neointimal or remodeling responses of the artery to balloon catheter injury in a nonhuman primate model (Geary et al., 1996). This apparent contradiction is probably due to substantial differences in experimental design. Previous studies utilized nonatherosclerotic animals, which have limited relevance to the clinical situation where response of vessels with advanced atherosclerosis is involved. It is now clear that compounds effective in preventing myointimal response to arterial injury in nonatherosclerotic animals have typically been ineffective in preventing restenosis in clinical trials. Among possible explanations for this incongruence are species differences in smooth muscle migration or proliferation, or differences in responses of atherosclerotic and nonatherosclerotic arteries. Furthermore, the endpoints typically addressed in animal studies, i.e., intimal proliferation and mass, may be minor determinants of restenosis in human patients.
