Nordestgaard B G, Tybjaerg-Hansen A, Lewis B
Department of Chemical Pathology and Metabolic Disorders, United Medical School, St. Thomas's Hospital, London, UK.
Arterioscler Thromb. 1992 Jan;12(1):6-18. doi: 10.1161/01.atv.12.1.6.
To compare the atherogenic potential of low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) under conditions where plasma levels of these lipoproteins are elevated, the influx of cholesterol in these lipoproteins into the aortic intima was measured in vivo in genetically hyperlipidemic rabbits from the St. Thomas's Hospital strain, an animal model that shares many of the features of the human disorder familial combined hyperlipidemia. Univariate linear regression showed that the arterial influx of LDL cholesterol (n = 25), IDL cholesterol (n = 14), and VLDL cholesterol (n = 10) was positively and linearly associated with plasma concentrations of LDL cholesterol in the range 0.2-6.4 mmol/l, of IDL cholesterol in the range 0.1-7.0 mmol/l, and of VLDL cholesterol in the range 0.7-8.5 mmol/l, respectively, and also with the extent of lesions in the arterial intima in the range 0-100% of the surface area. Multiple linear regression suggested that the arterial influx of LDL, IDL, and VLDL cholesterol was linearly dependent on plasma concentration, independent of lesion size. Furthermore, it appeared that the arterial influx of the three lipoproteins was linearly dependent on the extent of the lesions, independent of lipoprotein concentration. When influx was normalized for plasma concentration (intimal clearance) and for lesion size (compared within the same aorta), the intimal clearance of the larger IDL and VLDL particles was 15-35% less than that of the smaller LDL particles. These findings suggest that the quantitatively most important mechanism for transfer of plasma lipoproteins into the arterial intima involves nonspecific molecular sieving and that at elevated plasma levels, IDL and VLDL share with LDL the potential for causing atherosclerosis.
为了比较低密度脂蛋白（LDL）、中间密度脂蛋白（IDL）和极低密度脂蛋白（VLDL）在这些脂蛋白血浆水平升高情况下的致动脉粥样硬化潜力，在来自圣托马斯医院品系的遗传性高脂血症兔体内测量了这些脂蛋白中的胆固醇流入主动脉内膜的情况，该动物模型具有人类疾病家族性混合性高脂血症的许多特征。单变量线性回归显示，LDL胆固醇（n = 25）、IDL胆固醇（n = 14）和VLDL胆固醇（n = 10）的动脉流入量分别与血浆中LDL胆固醇浓度在0.2 - 6.4 mmol/L范围内、IDL胆固醇浓度在0.1 - 7.0 mmol/L范围内以及VLDL胆固醇浓度在0.7 - 8.5 mmol/L范围内呈正线性相关，并且还与动脉内膜病变范围在表面积的0 - 100%范围内呈正线性相关。多元线性回归表明，LDL、IDL和VLDL胆固醇的动脉流入量线性依赖于血浆浓度，与病变大小无关。此外，似乎这三种脂蛋白的动脉流入量线性依赖于病变范围，与脂蛋白浓度无关。当将流入量按血浆浓度（内膜清除率）和病变大小（在同一主动脉内进行比较）进行标准化时，较大的IDL和VLDL颗粒的内膜清除率比小的LDL颗粒低15 - 35%。这些发现表明，血浆脂蛋白转移到动脉内膜的数量上最重要的机制涉及非特异性分子筛分，并且在血浆水平升高时，IDL和VLDL与LDL一样具有引发动脉粥样硬化的潜力。
