GROWTH-FACTORS AND ATHEROSCLEROSIS

Normal blood vessel walls are composed of several layers of highly dif ferentiated smooth muscle cells that express specific proteins, such a s smooth muscle cell alpha actin that mark the differentiated state. B oth chemical and mechanical stimuli initiate a series of events that l ead to dedifferentiation of these cells, followed by neointima formati on and luminal narrowing, This process is initiated by the migration a nd proliferation of smooth muscle cells that cross the internal elasti c lamina and form the core of the atherosclerotic plaque, Neointima al so contains other cell types not normally present in the vessel walls, such as macrophages and T-cells, Deposition of extracellular matrix b y intimal cells may contribute to the luminal narrowing and loss of no rmal vascular remodeling, Chronic sustained injuries that occur in dia betes, such as abnormal lipoprotein profiles, oxidative stress, and in creased shear caused by hypertension, may contribute to the pathologic al release of growth factors that stimulate all three of these process es, The role of the integrin receptors that mediate not only macrophag e adhesion to blood vessels and migration but smooth muscle cell migra tion and proliferation as well, is currently being elucidated, Coopera tivity between growth factors and integrin ligands may be an important mechanism by which abnormal smooth muscle cell proliferation is susta ined, Several pathophysiological events that occur in diabetes, such a s chronic hyperglycemia, hyperinsulinemia, and abnormal lipoprotein pr ofiles, may contribute to a sustained pathological release of growth f actors that result in a perpetuation of these processes, Strategies to determine how interfering with growth factor action can partially rev erse some of these abnormalities and either attenuate or reverse neoin timal formation are being actively pursued.