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

• Published in: Diabetes (New York, N.Y.) Vol. 60; no. 10; pp. 2617 - 2623
• Main Authors: Morgantini, Cecilia, Natali, Andrea, Boldrini, Beatrice, Imaizumi, Satoshi, Navab, Mohamad, Fogelman, Alan M., Ferrannini, Ele, Reddy, Srinivasa T.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2011
• Subjects: Aged; Analysis; Anti-Inflammatory Agents - metabolism; Antioxidants; Antioxidants - metabolism; Apolipoproteins; Atherosclerosis; Biological and medical sciences; Blood & organ donations; Cardiovascular diseases; Care and treatment; Case-Control Studies; Cell-Free System; Complications and side effects; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Diet therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Fatty Acids - metabolism; Female; Genetic aspects; High density lipoprotein; High density lipoproteins; Humans; Internal medicine; Lipids; Lipoproteins; Lipoproteins, HDL - metabolism; Male; Medical sciences; Middle Aged; Oxidation; Patient outcomes; Peptides; Pharmacology and Therapeutics; Physiological aspects; Plasma; Prevention; Research design; Risk factors; Serum Amyloid A Protein; Type 2 diabetes; United States; Endocrinopathy; Type 2 diabetes; Metabolic diseases; Antioxidant
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db11-0378

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.