University of Arizona College of Medicine, Phoenix Campus, Phoenix, AZ, USA.
Eur J Clin Invest. 2012 Jul;42(7):709-16. doi: 10.1111/j.1365-2362.2011.02636.x. Epub 2012 Jan 31.
Accelerated cholesteryl ester transfer (CET) in patients with types 1 (T1D) and 2 diabetes enhances the atherogenicity of the apoB-containing CE acceptor lipoproteins. The study of lipoprotein density fractions cannot identify which of the five immunologically distinct apoB subclasses function as CE acceptors because they are heterogeneous and present in very low-, intermediate- and low density lipoproteins (VLDL, IDL and LDL, respectively). In order to design lipid-modifying therapies that specifically target these CE-enriched lipoprotein particles, it is necessary to first characterize their CE acceptor function.
To identify the CE acceptors, we estimated CE net mass transfer to the apoB subclasses LpB:C, LpB:E + LpB:C:E, LpB and LpAII:B:C:D:E from changes in neutral lipids measured by gas chromatography following their separation by sequential immunoaffinity chromatography in the plasma of 12 patients with T1D and six control subjects. In both groups, CE was distributed equally to LpB:E + LpB:C:E and LpB:C. In the T1D CE acceptors, however, both the magnitude of the increase (18% vs. 10%; P < 0·01) and the per particle mass of CE transferred were significantly greater than in controls (T1D: 2·29 μmol ± 2·1 vs. control 0·43 ± 0·43/mg apoB; P < 0·047).
While LpB:E + LpB:C:E and LpB:C functioned as CE acceptors in both groups, these subclasses increased their CE content to a greater degree and accrued more CE per particle in the patients with T1D. As this disturbance in lipoprotein remodelling may increase the cholesterol burden and potential atherogenicity of these apoB subclasses, it may be a previously unrecognized factor that increases cardiovascular risk in patients with T1D.
1 型（T1D）和 2 型糖尿病患者的胆固醇酯转移（CET）加速，增强了载 apoB 的胆固醇酯接受脂蛋白的动脉粥样硬化性。脂蛋白密度分数的研究不能确定五种免疫上不同的 apoB 亚类中的哪一种作为胆固醇酯接受体发挥作用，因为它们是异质的，存在于极低密度脂蛋白（VLDL）、中间密度脂蛋白（IDL）和低密度脂蛋白（LDL）中。为了设计专门针对这些富含胆固醇酯的脂蛋白颗粒的脂质修饰疗法，首先需要确定它们的胆固醇酯接受功能。
为了鉴定胆固醇酯接受体，我们通过气相色谱法估计了胆固醇酯净质量转移到 apoB 亚类 LpB:C、LpB:E+LpB:C:E、LpB 和 LpAII:B:C:D:E，方法是在通过顺序免疫亲和色谱法将其从 12 例 T1D 患者和 6 例对照者的血浆中分离出来后，测量中性脂质的变化。在两组中，胆固醇酯均匀分布在 LpB:E+LpB:C:E 和 LpB:C 上。然而，在 T1D 的胆固醇酯接受体中，增加的幅度（18%对 10%；P<0·01）和转移的每颗粒胆固醇酯质量都明显大于对照组（T1D：2·29μmol±2·1 对对照 0·43±0·43/mg apoB；P<0·047）。
虽然 LpB:E+LpB:C:E 和 LpB:C 在两组中都作为胆固醇酯接受体，但这些亚类增加了它们的胆固醇酯含量，并且在 T1D 患者中每颗粒胆固醇酯的含量更高。由于这种脂蛋白重塑的紊乱可能增加这些 apoB 亚类的胆固醇负担和潜在的动脉粥样硬化性，因此它可能是增加 T1D 患者心血管风险的一个以前未被认识的因素。
