The overall objective of this proposal is to identify the component(s) (i.e., specific isoflavones or peptide fractions) of soy that account for its protective effects on the cardiovascular system, assess their relative bioactivity and study mechanisms of action. The five following questions will be addressed: (1) what are the constituents of soy protein that account for its beneficial effects or atherogenesis; (2) which isoflavones (i.e., genistein or daidzein) contribute to soy's favorable effects on vasomotor function and atherosclerosis; (3) do the effects of soy depend on isoflavone peptide or isoflavone estrogen interactions; (4) what amounts of specific isoflavones and estrogen are needed to elicit and optimize these effects; and (5) what are the relative roles of estrogen receptor dependent and independent processes in mediating the cardioprotective effects of soy? To study the separate and combined effects of many components of soy on the development of atherosclerotic plaques, which cannot be studied easily in human subjects and nonhuman primates, mice with induced genetic mutations that result in increased susceptibility to the development of atherosclerosis and/or a deficiency in estrogen receptors will be used. The studies proposed will evaluate the role of the individual constituents of soy and their possible interactive effects in mediating the major cardioprotective effects that have been reported for soy. The results will further advance understanding of soy's cardioprotective properties and lead to strategies for optimizing its favorable effects.
