Braschi S, Geoffrion M, Nguyen A, Gaudreau Y, Milne R W
Endocrinology Division, Medicine Department, University of Ottawa, Ottawa Hospital, Riverside Campus, 1967 Riverside Drive, Ottawa, ON, K1H 7W9, Canada.
Diabetologia. 2006 Jun;49(6):1394-401. doi: 10.1007/s00125-006-0217-4. Epub 2006 Apr 4.
AIMS/HYPOTHESIS: When LDLs are exposed to glucose in vitro, glycation of apolipoprotein B100 (apoB) leads to a loss in its affinity for the LDL receptor and reproducible alterations in the immunoreactivity of specific apoB epitopes, including several epitopes close to the LDL receptor binding site. The aim of this work was to determine if similar immunological changes are observed in vivo in LDLs of diabetic and end-stage renal disease (ESRD) patients.
SUBJECTS, MATERIALS AND METHODS: The immunoreactivity of LDLs isolated from 14 diabetic patients with normal renal function and 13 patients with ESRD was studied with a panel of 25 well-characterised anti-apoB monoclonal antibodies.
Although diabetic and ESRD LDLs showed evidence of glycation modification, none of the changes in the apoB immunoreactivity induced by glucose in vitro was observed in vivo, including those for epitopes close to the LDL receptor binding domain.
CONCLUSIONS/INTERPRETATION: These results suggest that in vivo glycation of LDLs is a complex process that is not mimicked by in vitro exposure of LDLs to high concentrations of glucose. This questions the clinical significance of the in vitro glycation studies used to understand the pathophysiological consequences of LDL glycation in diabetes and ESRD.
目的/假设：当低密度脂蛋白（LDL）在体外与葡萄糖接触时，载脂蛋白B100（apoB）的糖基化会导致其对LDL受体的亲和力丧失，以及特定apoB表位免疫反应性的可重复性改变，包括几个靠近LDL受体结合位点的表位。这项研究的目的是确定在糖尿病和终末期肾病（ESRD）患者的LDL中，在体内是否观察到类似的免疫变化。
对象、材料和方法：使用一组25种特征明确的抗apoB单克隆抗体，研究了从14名肾功能正常的糖尿病患者和13名ESRD患者中分离出的LDL的免疫反应性。
尽管糖尿病和ESRD患者的LDL显示出糖基化修饰的证据，但在体内未观察到葡萄糖在体外诱导的apoB免疫反应性的任何变化，包括靠近LDL受体结合域的表位的变化。
结论/解读：这些结果表明，LDL的体内糖基化是一个复杂的过程，LDL在体外暴露于高浓度葡萄糖并不能模拟这一过程。这对用于理解糖尿病和ESRD中LDL糖基化病理生理后果的体外糖基化研究的临床意义提出了质疑。
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