Pathophysiology of high remnant lipoproteinemia underlying atherosclerotic disease in Japan and development of a new assay for remnant lipoproteins

最近的研究表明，乳糜微粒残余物清除受损可引起餐后高脂血症（PPHL），这可能是冠心病（CHD）的危险因素之一。此外，在发达国家，代谢综合征（内脏脂肪综合征）中极低密度脂蛋白（VLDL）残余物的增加是预防冠心病的重要治疗靶点。然而，血清残留浓度的测量仍然很复杂，目前还没有能够在自动分析仪上工作的系统。在本研究中，我们开发了一种新的血清残余胆固醇检测方法，并探讨了其在PPHL中的意义。用专用洗涤剂和磷脂酶D对血清中残余脂蛋白进行选择性匀浆，酶法测定胆固醇含量为残余脂蛋白-胆固醇（RemL-C）。健康对照组（n=39）、IIa型（Ha型HL， n=3）和IIb型HL， n=6)高脂蛋白血症患者。IIa型和IIb型HL在阿托伐他汀治疗（10 mg/天）前后进行口服脂肪负荷试验（30 g脂肪/m^2），为期4周。此外，我们使用凝胶过滤分析高甘油三酯血症血清。用化学发光法测定载脂蛋白B-48浓度，采用自制的载脂蛋白B-48单克隆抗体。在健康对照中，RemL-C的平均空腹值（mean）和标准差（SD）分别为3.4和1.4 mg/dL。lib HL的RemL-C高于正常范围（MEAN + 2SD）。口服脂肪负荷试验结果显示，在IIa和lib HL中，RemL-C峰值晚于TG峰值1或2 h。阿托伐他汀治疗可显著降低TG和RemL-C曲线下面积，尤其是在IIb HL中。在凝胶过滤分析中，在所谓的大VLDL的位置观察到RemL-C的峰值，并且与apoB-48的峰值一致。这些发现表明，我们的分析提供了一个简单的方案，一般用于残余胆固醇的测量。发现阿托伐他汀改善PPHL，至少部分通过与外源性脂蛋白代谢相关的机制。少

Recent studies have demonstrated that impaired clearance of chylomicron remnant causes postprandial hyper-lipidemia (PPHL), which suggested as one of the risk factors for coronary heart disease (CHD). Furthermore, the increase in very low density lipoprotein (VLDL) remnant in metabolic syndrome (visceral fat syndrome) is an important therapeutic target for the prevention of CHD in developed countries. The measurement of serum remnant concentrations, however, remains complicated and there are as yet no systems which can work on automated analyzers. In this study, we developed a new assay for serum remnant cholesterol using specific detergents and investigated its significance for PPHL.Remnant lipoproteins in serum were selectively homogenized by specific detergents and phospholipase D followed by enzymatic determination of cholesterol content as remnant lipoprotein-cholesterol (RemL-C). Healthy controls (n=39), type IIa (Ha HL, n=3), and type IIb HL, n=6) hyperlipoproteinemic patients w … More ere investigated. Type IIa and IIb HL were subjected to an oral fat loading test (30 g fat/m^2) before and after atorvastatin treatment (10 mg/day) for 4 weeks. Furthermore, we used gel filtration to analyze hypertriglyceridemic serum. The apolipoprotein (apo) B-48 concentrations were assessed with the chemiluminescence method using a monoclonal antibody to apoB-48 established by us.In healthy controls, the mean fasting value (MEAN) and standard deviation (SD) of RemL-C were 3.4 and 1.4 mg/dL, respectively. RemL-C of lib HL was higher than the normal range (MEAN + 2SD). Oral fat loading test results showed that in both IIa and lib HL, the RemL-C peaked 1 or 2 hrs behind the TG peak. Atorvastatin treatment reduced the area under the curve of TG and RemL-C drastically especially in IIb HL. In the gel filtra-tion analysis, the peak of RemL-C was observed at the position of so-called large VLDL and coincided with the peak of apoB-48. These findings demonstrate that our assay provides a simple protocol for general use for remnant cholesterol measurement. Atorvastatin was found to improves PPHL, at least partly through a mechanism associated with exogenous lipoprotein metabolism. Less