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

日本动脉粥样硬化性疾病高残留脂蛋白血症的病理生理学以及残留脂蛋白新检测方法的开发

基本信息

批准号：
16590455
负责人：
YAMAMURA Taku
金额：
$ 2.24万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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

近年来的研究表明，乳糜微粒残留清除障碍导致餐后高血糖（PPHL），是冠心病的危险因素之一。此外，极低密度脂蛋白（VLDL）残留在代谢综合征（内脏脂肪综合征）的增加是一个重要的治疗目标，在发达国家预防冠心病。然而，血清残留浓度的测量仍然是复杂的，并且还没有可以在自动分析仪上工作的系统。本研究建立了一种新的血清残余胆固醇测定方法，即用特异性洗涤剂和磷脂酶D选择性匀浆血清中的残余脂蛋白，然后用酶法测定残余脂蛋白-胆固醇（RemL-C）。健康对照组（n=39）、IIa型（Ha HL，n=3）和IIb型HL，n=6）高脂蛋白血症患者， ...更多信息在调查。在阿托伐他汀治疗（10 mg/天）前后，对IIa型和IIb型HL进行口服脂肪负荷试验（30 g脂肪/m^2），持续4周。此外，我们还采用凝胶过滤法分析了高血糖血清。采用化学发光法测定正常人血清载脂蛋白B-48（apoB-48）浓度，其空腹平均值（MEAN）为3.4 mg/dL，标准差（SD）为1.4 mg/dL。HL组RemL-C高于正常值（MEAN + 2SD）。口服脂肪负荷试验结果表明，在IIa和IIb HL中，RemL-C在TG峰后1或2小时达到峰值。阿托伐他汀治疗显著降低TG和RemL-C曲线下面积，尤其是IIb HL。在凝胶过滤分析中，在所谓的大VLDL位置观察到RemL-C峰，并且与apoB-48峰一致。这些发现表明，我们的测定提供了一个简单的协议，一般用于残余胆固醇测量。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