Studies on the cellular basis of atherosclerosis: the effects of atherosclerosis risk factors on platelets and the vascular endothelium.
Thrombosis is a well-recognized complication of atherosclerosis and may be a factor in initial lesion formation. Experimental endothelial cell injury results in activation of the coagulation mechanism and therefore may be a critical aspect of the pathogenesis of occlusive vascular disease. If this is so, then risk factors for atherosclerosis should affect the endothelium either by causing cell injury, inhibiting repair mechanisms, or altering its thromboresistant properties. To test this, we studied the effect of several risk factors on endothelial cell behavior in vitro. Since the smooth muscle cell is the major cellular component of human atherosclerotic plaque and since a primary smooth muscle cell lesion is suggested by the clonal nature of human plaque, we also studied the effect of risk factors on arterial smooth muscle behavior. We have found that homocysteine directly injures human endothelium, which may account for the premature arterial disease in homocystinuria. Serum from patients with familial hypercholesterolemia inhibits the critical function of endothelial cell migration, as well as arterial smooth muscle cell migration. Moderate hypoxia has no effect on endothelial cell or smooth muscle cell viability, proliferation, or migration. Platelet factors are shown to affect human smooth muscle cell proliferation and both endothelial cell and smooth muscle cell migration. Preliminary study of platelet activation in diabetes with retinopathy suggests a relation to glucose control, but might reflect underlying vessel disease rather than direct platelet effect.
D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology; D001792:Blood Platelets / Q000502:physiology*; D003925:Diabetic Angiopathies / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000150:complications; D006712:Homocystinuria / Q000150:complications; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D000860:Hypoxia / Q000150:complications; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D012306:Risk