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动脉粥样硬化的保护中起着重要作用，而高密度脂蛋白的缺乏会导致动脉粥样硬化的过早发生。然而，我们已经报道了某些类型的高密度脂蛋白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高密度脂蛋白缺乏的角膜混浊。在本研究中，我们发现了高密度脂蛋白血症伴胆固醇酯转移蛋白(CETP)缺乏的病例，并对这种代谢紊乱中的脂蛋白代谢进行了研究，以阐明CETP在动脉粥样硬化预防系统中的生理作用。高密度脂蛋白小球明显增大，胆固醇酯(CE)和载脂蛋白E含量较高。也就是说，颗粒变得多分散，由两个大小不同的组组成。这些结果提示，CETP可能在将CE从高密度脂蛋白转移到低密度脂蛋白并形成成熟、均一的低密度脂蛋白过程中起重要作用，这一过程的缺陷可能导致胆固醇从外周组织到肝脏的转运系统，最终导致组织对脂质储存的预防受到损害。

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.