Soy and Heart Disease Prevention: Potential Mechanisms Unrelated to Cholesterol Reduction Biology of Atherosclerotic Plaque Formation: Possible Role of Growth Factors in Lesion Development and the Potential Impact of Soy1

occlude the affected artery by increasing the thickness of the intima. The focal thickening of the intima is due to a large increase in smooth muscle cells, formation of new connective tissue matrix by these smooth mus cle cells and, in hyperlipidemic individuals, the accu mulation of intracellular and extracellular lipid. Addi tionally, monocytes and T lymphocytes infiltrate the artery wall. Various forms of "injury " may lead to cel lular infiltration and proliferation. Localized cellular in filtration of monocytes and T cells may be due to changes in adhesive properties of the endothelial sur face, involving the expression of specific adhesion mol ecules. The directed cell migration and proliferation may represent the cells ' response to polypeptide growth factors, acting singly or in concert. These peptide growth factors also modulate matrix synthesis and degradation, angiogenesis, cell-cell adhesion and cel lular metabolism, including lipid uptake. In atheroscle rosis, growth factors may be delivered by infiltrating cells or by activation of cells within the artery wall. Normally, growth factors and their cell-surface recep tors are expressed at low or undetectable levels. Their up-regulation in early and developing atherosclerotic lesions suggests a pathogenic role for these molecules. Increased levels of isoflavonoids, in particular genistein, which are associated with consumption of soy-based diets, inhibit cell adhesion, alter growth factor activity and inhibit cell proliferation involved in lesion formation