Biology of atherosclerotic plaque formation: possible role of growth factors in lesion development and the potential impact of soy.
The advanced lesions of atherosclerosis 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 muscle cells and, in hyperlipidemic individuals, the accumulation of intracellular and extracellular lipid. Additionally, monocytes and T lymphocytes infiltrate the artery wall. Various forms of "injury" may lead to cellular infiltration and proliferation. Localized cellular infiltration of monocytes and T cells may be due to changes in adhesive properties of the endothelial surface, involving the expression of specific adhesion molecules. 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 cellular metabolism, including lipid uptake. In atherosclerosis, growth factors may be delivered by infiltrating cells or by activation of cells within the artery wall. Normally, growth factors and their cell-surface receptors 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.
Raines
E W
EW
Department of Pathology, University of Washington, Seattle.
Ross
R
R
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004044:Dietary Proteins / Q000494:pharmacology; D019833:Genistein; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D014674:Plant Proteins, Dietary / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D030262:Soybean Proteins; D013025:Glycine max
D004044:Dietary Proteins; D006131:Growth Inhibitors; D006133:Growth Substances; D007529:Isoflavones; D014674:Plant Proteins, Dietary; D030262:Soybean Proteins; D019833:Genistein; D011505:Protein-Tyrosine Kinases