We have identified two cholesterol-rich lipid particles, one rich in unesterified cholesterol and the other rich in esterified cholesterol in the extracellular space of human atherosclerotic lesions. The purpose of this project is to study the chemical and structural properties of these two cholesterol-rich particles and to determine their roles in vascular lipid deposition. The unesterified cholesterol-rich lipid particles have a hydrated density of 1.02-1.06 g/ml (peak at 1.036 g/ml). They have a high molar ratio of unesterified cholesterol to phospholipid (2.6:1) and 76% of particle cholesterol is unesterified. The esterified cholesterol-rich particles have a hydrated density of less than 1.01 g/ml. These particles also have a 2.6:1 molar ratio of unesterified cholesterol to phospholipid, but 72% of particle cholesterol is esterified. The phospholipid classes and cholesteryl ester fatty acid composition of the two lipid particles are similar. The predominant phospholipids are sphingomyelin(55%) and phosphatidylcholine (27%). Both particles contain substantial amounts of lysophosphatidylcholine (7-9%). Phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine are present in trace amounts. The major fatty acids in lipid particle cholesteryl esters are palmitate(20%), oleate(30%), and linoleate (30%). Both particles have diameters between 70 and 300 nm. The unesterified cholesterol-rich particles are spherical and vesicular and show uni- and multilamellar structures. The esterified cholesterol-rich particles are very small lipid droplets often demonstrating pitting (possible sites of lipolysis) at their surface. The two cholesterol-rich particles we have isolated appear to represent an early pathologic form of cholesterol that accumulates in the vessel wall during atherogenesis. Studies of the origin and fate of these particles will contribute to a better understanding of the atherosclerotic disease process.
