title: Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function.
abstract: BACKGROUND
  High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D).
  
  
  OBJECTIVE
  The objective of our study was to investigate the effects of in vitro glycoxidized HDL and HDL from patients with T2D on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL.
  
  
  RESULTS
  Compared with control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to scavenger receptor BI (SR-BI). Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phosphatidylcholine (PC), namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE, and 15-HETE in phospholipids (2.1-, 2.1-, and 2.4-fold increase, respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI.
  
  
  CONCLUSIONS
  Our results suggest that in vitro glycoxidized HDL as well as HDL from patients with T2D inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from patients with T2D.
authors: Institut National de la Santé et de la Recherche Médicale (Q.H.L., E.V., M.G., M.L., P.M., C.C.), UMR 1060, Laboratoire Cardiovasculaire, Métabolisme, Diabétologie, et Nutrition, Université de Lyon, UMR 1397 Institut National de la Recherche Agronomique, Institut National des Sciences Appliquées de Lyon (INSA-Lyon), IMBL, 69621 Villeurbanne, France; Laboratoire de Chimie Organique et Bioorganique (M.E.A., L.S.), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR 5246 Centre National de la Recherche Scientifique, INSA-Lyon, Villeurbanne, France; and Fédération d'Endocrinologie (B.S., P.M.), Hospices Civils de Lyon, 69677 Lyon Bron, France.
authors: Quang Huy
authors: QH
authors: Lê
authors: Meddy
authors: M
authors: El Alaoui
authors: Evelyne
authors: E
authors: Véricel
authors: Bérénice
authors: B
authors: Ségrestin
authors: Laurent
authors: L
authors: Soulère
authors: Michel
authors: M
authors: Guichardant
authors: Michel
authors: M
authors: Lagarde
authors: Philippe
authors: P
authors: Moulin
authors: Catherine
authors: C
authors: Calzada
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008075:Lipoproteins, HDL; D010743:Phospholipids; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium