Studies on the Preventive System Against Atherosclerosis Based on the Discovery of Cases With Choles-Terol Ester Transfer Protein Deficiency.

高密度脂蛋白被认为在保护动脉粥样硬化中起重要作用，HDL的缺乏导致过早的动脉粥样硬化。然而，我们已经报道了某些类型的高HDL胆固醇血症可能伴随着脂质储存，包括冠状动脉粥样硬化和类似于HDL缺乏的角膜混浊。在本研究中，我们发现了高HDL胆固醇血症与胆固醇酯转移蛋白（CETP）缺乏的情况下，研究这种代谢紊乱的脂蛋白代谢，以阐明CETP在预防动脉粥样硬化系统中的生理作用。结果显示，HDL蛋白酶活性明显增高，胆固醇酯（CE）和载脂蛋白E含量增高。我们证明，LDL戊环也成为异常的CETP缺乏症。也就是说，颗粒变得多分散，并由大小不同的两组组成。提示CETP可能在胆固醇从HDL向LDL的转运及形成成熟、均一的LDL过程中起重要作用，这一过程的缺陷可能导致胆固醇从外周组织向肝脏转运系统的障碍，最终导致组织对脂质储存的防御功能受损。

High density lipoprotein has been believed to play an important role in protecting atherosclerosis and the deficiency of HDL causes premature atherosclerosis. However, we have reported some types of hyper HDL cholesterolemia may be accompanied with lipid storage including coronary atherosclerosis and corneal opacities similar to HDL deficiency. In this study, we found the cases with hyper HDL cholesterolemia with Chdesterol Ester Transfer Protein (CETP) deficiency and studied the lipoprotein metabolism in this metabolic disorder to clarify physiological roles of CETP in the preventive system against atherosclerosis. HDL pasticles were shown to be markidly enlarged with high content of cholesteryl ester (CE) and apolipoprotein E. We demonstrated that LDL penticles also became abnormal in CETP deficiency. Namely, particles became polydisperse and consist of two groups different in size. These result suggests that CETP may play an important role in transferring CE from HDL to LDL and forming mature and homogeneous LDL.The defect of this process may result in cholesterol transport system from peripheral tissues to liver and finally cause the impairment of prevention against lipid storage in tissues.