Chao F F, Blanchette-Mackie E J, Dickens B F, Gamble W, Kruth H S
Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
J Lipid Res. 1994 Jan;35(1):71-83.
Previously, we isolated and characterized unesterified cholesterol-rich lipid particles (UCLP) that accumulate in extracellular spaces of atherosclerotic lesions of humans and cholesterol-fed rabbits. In the present study, we examined early developing atherosclerotic lesions to determine when UCLP appear and when they become enriched in cholesterol and sphingomyelin. Cholesterol-fed NZW rabbits, which rapidly develop atherosclerotic lesions, and genetically hyperlipidemic WHHL rabbits, which develop lesions over a longer period of time, were studied. UCLP of peak density 1.04 g/ml appear as early as 4 weeks after the onset of cholesterol feeding and progressively accumulate during atherosclerotic lesion development. Beginning with their appearance and afterwards, UCLP contain a saturating level (2:1 molar ratio) of cholesterol relative to phospholipid. Whereas, early UCLP are enriched in phosphatidylcholine, with time UCLP become enriched with sphingomyelin. Another UCLP population having a peak density of 1.09 g/ml was present in control aortas and increased in amount more slowly than the d 1.04 g/ml UCLP during cholesterol feeding. The d 1.09 g/ml particles were predominantly unilamellar vesicles, the majority between 100 and 200 nm in diameter. They contained > 90% of their cholesterol in unesterified form and their ratio of unesterified cholesterol to phospholipid progressively increased from 0.6 to 1.7 during cholesterol feeding. Liposome resistance to solubilization by high density lipoproteins is known to be increased by enrichment with unesterified cholesterol and sphingomyelin. Sphingomyelin enrichment of unesterified cholesterol-rich lipid particles (UCLP) could stabilize cholesterol in a form that does not readily crystallize. However, at the same time, the early and progressive accumulation of UCLP in developing atherosclerotic lesions may limit reverse cholesterol transport and accelerate disease progression.
此前，我们分离并鉴定了富含未酯化胆固醇的脂质颗粒（UCLP），这些颗粒积聚在人类和喂食胆固醇的兔子动脉粥样硬化病变的细胞外间隙中。在本研究中，我们检查了早期发展的动脉粥样硬化病变，以确定UCLP何时出现以及何时富含胆固醇和鞘磷脂。研究了喂食胆固醇后迅速发展为动脉粥样硬化病变的新西兰白兔（NZW），以及在较长时间内发展为病变的遗传性高脂血症WHHL兔。密度峰值为1.04 g/ml的UCLP早在喂食胆固醇4周后就出现，并在动脉粥样硬化病变发展过程中逐渐积累。从其出现开始，UCLP相对于磷脂含有饱和水平（2:1摩尔比）的胆固醇。早期的UCLP富含磷脂酰胆碱，随着时间的推移，UCLP富含鞘磷脂。另一种密度峰值为1.09 g/ml的UCLP群体存在于对照主动脉中，在喂食胆固醇期间其数量增加的速度比密度为1.04 g/ml的UCLP慢。密度为1.09 g/ml的颗粒主要是单层囊泡，大多数直径在100至200 nm之间。它们所含胆固醇的90%以上为未酯化形式，在喂食胆固醇期间，其未酯化胆固醇与磷脂的比例从0.6逐渐增加到1.7。已知通过富含未酯化胆固醇和鞘磷脂可增加脂质体对高密度脂蛋白溶解的抗性。富含未酯化胆固醇的脂质颗粒（UCLP）的鞘磷脂富集可以稳定胆固醇，使其不易结晶。然而，与此同时，UCLP在发展中的动脉粥样硬化病变中早期和逐渐积累可能会限制胆固醇逆向转运并加速疾病进展。
