Anti-inflammatory and Antioxidant Properties of HDLs Are Impaired in Type 2 Diabetes

Abstract

OBJECTIVEIn 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 METHODSHDL 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.RESULTSThe 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).CONCLUSIONSIn patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired.

Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia

“…38, 43 Morgantini et al reported that the anti-inflammatory properties of HDL were impaired in patients with T2DM. 44 Consistent with these findings, the present study showed that inflammatory markers such as hsCRP and lipoprotein (a) were higher in patients than in healthy controls. Lipoprotein (a) has proatherogenic and prothrombotic effects.…”

Dysfunctional HDL: From Structure-Function-Relationships to Biomarkers

“…However, HDL from patients with CAD on statin therapy remained proinflammatory when compared to HDL from healthy subjects, despite a significant improvement in plasma lipid levels. Interestingly, impaired antioxidant properties and increased oxidized fatty acids content were found in HDL from patients with type 2 diabetes (Morgantini et al 2011). The authors speculated that the elevated levels of oxidized fatty acids in HDL from these patients may account for the impaired antioxidant properties of the lipoprotein (Morgantini et al 2011).…”

“…Interestingly, impaired antioxidant properties and increased oxidized fatty acids content were found in HDL from patients with type 2 diabetes (Morgantini et al 2011). The authors speculated that the elevated levels of oxidized fatty acids in HDL from these patients may account for the impaired antioxidant properties of the lipoprotein (Morgantini et al 2011). Moreover, in a different study, the ability of HDL to prevent LDL oxidation was found to be reduced in patients with acute coronary syndrome but not in patients with stable coronary artery syndrome (Patel et al 2011).…”

Impact of Cigarette Smoking Cessation on High-Density Lipoprotein Functionality

“…14, 15 Furthermore, it has been reported that the antiinflammatory and antioxidative capacities of HDL were impaired in patients with diabetes mellitus type 2. 16 It is well known that HDL may be modified and lose its atheroprotective effects under chronic inflammation (ie, it can exhibit functional or dysfunctional properties). 17-19 It has been reported that markers of functional HDL are apolipoprotein A-I (apoA-I) and paraoxonase1, and those of dysfunctional HDL are apoC-III, serum amyloid A1 and lipoprotein-associated phospholipase A2 (Lp-PLA2).…”