OBJECTIVE-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. RESEARCH DESIGN AND METHODS-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. RESULTS-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). CONCLUSIONS-In patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired. Diabetes 60:2617-2623, 2011
Anti-inflammatory and Antioxidant Properties of HDLs Are Impaired in Type 2 Diabetes
NATALI, ANDREA;FERRANNINI, ELEUTERIO;
2011-01-01
Abstract
OBJECTIVE-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. RESEARCH DESIGN AND METHODS-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. RESULTS-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). CONCLUSIONS-In patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired. Diabetes 60:2617-2623, 2011I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
