Basic aspects of the pathogenesis of human atherosclerosis

Abstract

Labeled antibodies have been used to study the role of plasma beta-lipoprotein in atherosclerosis with the light and electron microscope. Beta-lipoprotein circulates with the blood and diffuses through the arterial wall to be picked up in the lymph. It enters the smooth muscle cells of the arterial wall apparently to take part in lipid energy metabolism. Selected areas of the arterial intima accumulate large quantities of beta-lipoprotein in both intra- and extracellular locations, playing a role in the production of the atherosclerotic lesion. Most of the lipid in the plaque stains as beta-lipoprotein. Enzyme histochemical studies show loss of activity of adenosine triphosphatase and in the oxidation of malate and of fatty acid in the areas of lipid accumulation. There appears to be a specific loss of membrane-associated adenosinetriphosphatase, possibly interfering with transport of lipids into and within the cell. Similar accumulations of beta-lipoprotein have been shown to occur in fatty degeneration of smooth muscle in a leiomyoma and in fatty degeneration of cardiac muscle adjacent to myocardial infarction. These findings suggest that failure of the arterial wall to metabolize lipids transported as plasma beta-lipoprotein is a basic cause of atherosclerosis.