Tsimikas S, Palinski W, Witztum J L
Division of Cardiovascular Diseases, Department of Medicine, University of California, San Diego, USA.
Arterioscler Thromb Vasc Biol. 2001 Jan;21(1):95-100. doi: 10.1161/01.atv.21.1.95.
Autoantibodies to oxidized low density lipoprotein (OxLDL) are elevated in some human populations with increased risk of atherosclerosis. To determine whether autoantibody levels to epitopes of OxLDL reflect the extent of aortic atherosclerosis and the content of OxLDL, we measured IgG and IgM autoantibody titers to malondialdehyde (MDA)-LDL and copper-oxidized LDL (Cu-OxLDL) in 43 LDL receptor-deficient mice consuming atherogenic and regression diets. Antibody titers were correlated to percent atherosclerotic surface area, aortic weight, and aortic OxLDL content, measured as the in vivo uptake of (125)I-MDA2, a monoclonal antibody to MDA-LDL. All mice were fed an atherogenic diet for 6 months, and 1 group was euthanized. The other 3 groups were fed an atherogenic diet (fat/CHOL group), normal mouse chow (chow group), or mouse chow supplemented with vitamins E and C (chow+VIT group) for an additional 6 months. After dietary intervention, compared with their own baseline, autoantibody titers to MDA-LDL and Cu-OxLDL increased significantly in the fat/CHOL group, whereas they did not change or decreased significantly in the chow and chow+VIT groups. Aortic weight and surface area showed significant progression in the fat/CHOL group, mild progression in the chow group, and no progression in the chow+VIT group (P<0.001), whereas OxLDL content actually decreased in the latter 2 groups (P<0.001). Significant correlations were seen with MDA-LDL autoantibody titers and OxLDL content (IgM, R=0.64 and P=0.0009; IgG, R=0.52 and P=0.009), as well as with percent surface area and aortic weight. These data support the hypothesis that autoantibody titers to OxLDL reflect changes in OxLDL content in atherosclerotic lesions of LDL receptor-deficient mice. Whether autoantibody titers to OxLDL will provide similar valuable insights into the extent of human atherosclerosis, particularly anatomic measurements of plaque burden and OxLDL content, remains to be determined.
在一些动脉粥样硬化风险增加的人群中，氧化型低密度脂蛋白（OxLDL）自身抗体水平会升高。为了确定针对OxLDL表位的自身抗体水平是否反映主动脉粥样硬化的程度以及OxLDL的含量，我们在43只食用致动脉粥样硬化饮食和回归饮食的低密度脂蛋白受体缺陷小鼠中，测量了针对丙二醛（MDA）-LDL和铜氧化LDL（Cu-OxLDL）的IgG和IgM自身抗体滴度。抗体滴度与动脉粥样硬化表面积百分比、主动脉重量以及主动脉OxLDL含量相关，后者通过针对MDA-LDL的单克隆抗体（125）I-MDA2的体内摄取来测量。所有小鼠先食用致动脉粥样硬化饮食6个月，然后对其中1组实施安乐死。另外3组分别再食用致动脉粥样硬化饮食（脂肪/胆固醇组）、正常小鼠饲料（饲料组）或补充了维生素E和C的小鼠饲料（饲料+维生素组）6个月。饮食干预后，与自身基线相比，脂肪/胆固醇组中针对MDA-LDL和Cu-OxLDL的自身抗体滴度显著升高，而饲料组和饲料+维生素组中这些滴度未改变或显著降低。脂肪/胆固醇组的主动脉重量和表面积有显著进展，饲料组有轻度进展，饲料+维生素组无进展（P<0.001），而后两组的OxLDL含量实际上有所下降（P<0.001）。MDA-LDL自身抗体滴度与OxLDL含量（IgM，R=0.64，P=0.0009；IgG，R=0.52，P=0.009）以及与表面积百分比和主动脉重量之间存在显著相关性。这些数据支持了这样一种假设，即针对OxLDL的自身抗体滴度反映了低密度脂蛋白受体缺陷小鼠动脉粥样硬化病变中OxLDL含量的变化。针对OxLDL的自身抗体滴度是否能为人类动脉粥样硬化的程度，特别是斑块负荷和OxLDL含量的解剖学测量提供类似的有价值见解，仍有待确定。
