Department of Microbial and Molecular Systems, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
J Lipid Res. 2010 Jun;51(6):1478-85. doi: 10.1194/jlr.M003509. Epub 2010 Jan 19.
To evaluate whether the relative atherogenicity of VLDL and LDL is dependent on the topographic site, atherosclerosis was compared at four topographic sites in homozygous LDL receptor (LDLr)-deficient rabbits fed normal chow and in heterozygous LDLr-deficient rabbits with the same genetic background fed a 0.15% cholesterol diet to match cholesterol levels. VLDL cholesterol was significantly higher and LDL cholesterol significantly lower in LDLr(+/-) diet rabbits compared with LDLr(-/-) rabbits. Intimal area in the ascending thoracic aorta and in the abdominal aorta at the level of the renal arteries was 1.4-fold (P < 0.05) and 1.5-fold (P < 0.05) higher, respectively, in LDLr(-/-) rabbits than in LDLr(+/-) diet rabbits, whereas no significant difference occurred in the descending thoracic aorta and in the abdominal aorta just above the bifurcation. Differences remained statistically significant after adjustment for plasma cholesterol, triglycerides, and sex. Compared with LDLr(+/-) diet rabbits, higher intimal lipoprotein lipase (LPL) and apolipoprotein (apo) B levels were observed in LDLr(-/-) rabbits only at the level of the descending thoracic aorta. Intimal apo E levels in LDLr(-/-) rabbits were significantly lower in sites with a larger intima than in LDLr(+/-) diet rabbits. In conclusion, the relative atherogenicity of VLDL and LDL is dependent on the topographic site.
为了评估 VLDL 和 LDL 的相对动脉粥样硬化作用是否取决于部位,在接受正常饮食的纯合 LDL 受体(LDLr)缺陷兔和接受相同遗传背景、含有 0.15%胆固醇饮食以匹配胆固醇水平的杂合 LDLr 缺陷兔的四个部位比较了动脉粥样硬化。与 LDLr(-/-)兔相比,LDLr(+/)饮食兔的 VLDL 胆固醇显著升高,LDL 胆固醇显著降低。升主动脉和肾动脉水平的腹主动脉内膜面积分别高出 LDLr(-/-)兔 1.4 倍(P<0.05)和 1.5 倍(P<0.05),而在降主动脉和腹主动脉分叉以上部位则无显著差异。经血浆胆固醇、甘油三酯和性别调整后,差异仍有统计学意义。与 LDLr(+/)饮食兔相比,仅在降主动脉部位观察到 LDLr(-/-)兔的内膜脂蛋白脂肪酶(LPL)和载脂蛋白(apo)B 水平显著升高。LDLr(-/-)兔的内膜 apoE 水平在较大的内膜部位显著低于 LDLr(+/)饮食兔。总之,VLDL 和 LDL 的相对动脉粥样硬化作用取决于部位。