title: Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes.
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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgantini
authors.forename: Andrea
authors.initials: A
authors.lastname: Natali
authors.forename: Beatrice
authors.initials: B
authors.lastname: Boldrini
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imaizumi
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D016022:Case-Control Studies; D002474:Cell-Free System; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010455:Peptides; D000685:Serum Amyloid A Protein
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005227:Fatty Acids; C472885:L-4F peptide; D008075:Lipoproteins, HDL; D010455:Peptides; D000685:Serum Amyloid A Protein