Cholesterol turnover in lipid phases of human atherosclerotic plaque.
The turnover of free cholesterol in atheromatous plaque lipid phases was studied in a patient undergoing peripheral vascular surgery. [14C]Cholesterol was injected intravenously 139 days prior to surgery, and [3H]cholesterol was injected 12 days pre-op. The plasma cholesterol specific radioactivity decay curves were determined from the times of isotope injection until surgery. At surgery, atheroma, skin, muscle, and tendon were obtained. Lipid phases of plaque homogenate were isolated by density gradient centrifugation. The top layer of the gradient, layer 1, contained the cholesteryl ester oil droplet phase, layer 2 was enriched in phospholipid bilayer phase, layer 3 contained cholesterol monohydrate crystals and the pellet, layer 4 had more dense plaque components such as collagen and elastin. The tissue:plasma specific radioactivity ratios on days 12 and 139 respectively were muscle, 0.86, 2.47; skin, 0.74, 1.20; tendon, 0.18, 1.45; total plaque, 0.22, 1.39; plaque layer 1, 0.31, 1.50; layer 2, 0.22, 1.53; layer 3, 0.08, 0.61; and layer 4, 0.20, 0.88. Thus, plaque atheroma, which contains physically distinct forms of cholesterol, had correspondingly different rates of cholesterol turnover. Cholesterol solubilized in liquid oil droplets (layer 1) and liquid crystalline phospholipid bilayers (layer 2) had specific radioactivity values similar to those of tendon cholesterol, and represented tissue cholesterol that was undergoing slow equilibration with the plasma cholesterol pool. Pellet cholesterol (layer 4), which is probably connective tissue-associated, had lower specific radioactivity values, well below those of plasma cholesterol even after 5 months. Crystalline cholesterol (layer 3) had the lowest specific radioactivity values of all tissues and plaque fractions. Therefore, cholesterol in the crystalline state is relatively inert. Since crystalline cholesterol can account for over 40% of plaque free cholesterol, resistance to mobilization of this lipid may be an important obstacle to plaque regression.
D000368:Aged; D001161:Arteriosclerosis / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D013997:Time Factors; D014018:Tissue Distribution
D002784:Cholesterol