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Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function

Quang Huy Lê 1 Meddy El Alaoui 2, 3 Evelyne Véricel 1 Bérénice Ségrestin 4 Laurent Soulère 2 Michel Guichardant 1 Michel Lagarde 1 Philippe Moulin 1, 4 Catherine Calzada 1, * 
* Corresponding author
2 COB - Chimie Organique et Bioorganique
ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
3 MEM² - Métabolisme, Enzymes et Mécanismes Moléculaires
ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
Abstract : CONTEXT: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 T2D patients on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL.RESULTS:Compared to 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 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 phospholipids, 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:Altogether, our results indicate that in vitro glycoxidized HDL as well as HDL from T2D patients inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from T2D patients.
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Submitted on : Tuesday, March 24, 2015 - 8:40:53 AM
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Quang Huy Lê, Meddy El Alaoui, Evelyne Véricel, Bérénice Ségrestin, Laurent Soulère, et al.. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function. Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2015, 100 (5), pp.1-10. ⟨10.1210/jc.2014-4214⟩. ⟨inserm-01134619⟩



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