Minireview: Estrogen and mouse models of atherosclerosis

The use of hormone replacement therapy for coronary heart disease prevention in humans has been an area of intense controversy. The atheroprotective qualities of estrogens have been challenged recently by several negative results of randomized clinical trials in postmenopausal women. However, the inhibitory effects of estrogens on atherogenesis are well documented in numerous animals, including atherosclerotic mouse models, but the detailed mechanisms of this protection are not understood. In this minireview, we will focus on the considerable success that has been achieved in demonstrating the atheroprotective effects of 17beta-estradiol in apolipoprotein E and low-density lipoprotein receptor-deficient mice and the use of these atherosclerotic mouse models in pharmacological and genetic study designs to investigate antiatherogenic mechanisms of estrogens. Mouse models of atherosclerosis should prove beneficial to understanding the cellular and molecular mechanisms of estrogen-mediated atheroprotection and aid the development of improved therapies to confer the benefits and reduce the risks associated with hormone replacement therapy.