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

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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