Department of Internal Medicine, University of Pisa, Pisa, Italy.
Diabetes. 2011 Oct;60(10):2617-23. doi: 10.2337/db11-0378. Epub 2011 Aug 18.
In mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL function, prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.
HDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography-tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.
The HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).
In patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired.
在小鼠中，载脂蛋白 A-I 模拟肽 4F 可恢复高密度脂蛋白（HDL）功能，预防糖尿病引起的动脉粥样硬化。我们旨在确定 2 型糖尿病（T2D）患者的 HDL 功能是否受损，以及 4F 治疗是否可改善 T2D 患者体外血浆中 HDL 的功能。
在 93 名 T2D 患者和 31 名对照者中，通过测试 HDL 抑制人主动脉内皮细胞单层中 LDL 诱导的单核细胞趋化活性的能力，来确定 HDL 的抗炎功能。使用不含 LDL 的细胞游离测定法测量 HDL 的抗氧化特性，该测定法使用二氯荧光素二乙酸盐。通过液相色谱-串联质谱法测量 HDL 中的氧化脂肪酸。在患者和对照者亚组中，在孵育 L-4F 后重复测定 HDL 炎症指数。
T2D 患者的 HDL 炎症指数为 1.42±0.29，而对照组为 0.70±0.19（P＜0.001）。与对照组相比，T2D 患者的细胞游离测定法受损（2.03±1.35 对 1.60±0.80，P＜0.05），并且 HDL 内在氧化（无 LDL 的细胞游离测定法）也较高（1708±739 对 1233±601 相对荧光单位，P＜0.001）。T2D 患者的所有测量氧化脂肪酸均明显升高。细胞游离测定值与 HDL 各部分中氧化脂肪酸的含量之间存在显著相关性。L-4F 治疗可恢复糖尿病血浆样本中的 HDL 炎症指数（从 1.26±0.17 降至 0.71±0.11，P＜0.001），并轻微影响健康受试者（从 0.81±0.16 降至 0.66±0.10，P＜0.05）。
在 T2D 患者中，氧化脂肪酸的含量增加，HDL 的抗炎和抗氧化活性受损。
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