ISOLATION AND CHARACTERIZATION OF LIPID-RICH PARTICLES IN ATHEROSCLEROTIC LESIONS

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The purpose of this project is to isolate and characterize unesterified cholesterol-rich lipid particles previously identified by us in atherosclerotic lesions using histochemical mecthods. Two major fractions of cholesterol-rich lipid particles were isolated from atherosclerotic aortas; one fraction has a density less than 2.00 with cholesterol mostly in an esterified form. The other fraction has a mean density of approximately 1.02 with cholesterolmostly in an unesterified form. Interestingly, we have found that sphingomyelin is the predominant phospholipid in the unesterified cholesterol-rich fraction. The identification of sphingomyelin as the predominant phospholipid associated with lesion unesterified cholesterol is an important new finding. From histochemical studiews, we know that these unesterified cholesterol-rich particles occur within cells and in the extracellular space. These particlews contain unesterified cholesterol that is less extractable than is normal plasma membrane unesterified cholesterol. Because large amounts of sphigomyelin also accumulatew in atherosclerotic vessels, and considering cholesterol's high affinity for sphingomyelin, we now have a theoretical basis to help explain the retention of unesterified cholesterol in atherosclerotic lesions. This finding cointributes to our understanding of cholesterol deposition and will be important for the development of drugs designed to remove the cholesterol from atherosclerotic lesions.