Atherosclerosis 203 (2009) 119–125 Alterations in the transfer of phospholipids from very-low density lipoproteins to activated platelets in type 2 diabetes Salam Ibrahim a,b,c,d,e , Nicolas Guillot a,b,c,d,e , Valérie Pruneta-Deloche a,b,c,d,e , Sybil Charrière a,b,c,d,e , Catherine Calzada a,b,c,d,e , Michel Guichardant a,b,c,d,e , Philippe Moulin a,b,c,d,e , Michel Lagarde a,b,c,d,e , Gabriel Ponsin a,b,c,d,e,∗ a INSERM, U870, IFR62, Lyon F-69008, France b INRA, UMR1235, Lyon F-69008, France c INSA-Lyon, RMND, Villeurbanne F-69621, France d Université Lyon 1, Lyon F-69003, France e Hospices Civils de Lyon, Lyon F-69008, France Received 7 January 2008; received in revised form 21 May 2008; accepted 21 May 2008 Available online 3 June 2008 Abstract Type 2 diabetes is a situation at high cardiovascular risk, characterized by platelet hyperactivation, oxidative stress, elevated very-low density lipoprotein (VLDL) and low high-density lipoprotein concentrations. In the present report, we describe the effects of these alterations on the transfers of phospholipids (PL) from VLDL to platelets in basal conditions or after thrombin (0.1 U/mL) or lipoprotein lipase (LPL, 500 ng/mL)-mediated platelet activation. In vitro transfer of radiolabelled PL from VLDL (200 M PL) to platelets (2 × 10 8 /mL) was measured after incubations of 1 h at 37 ◦ C in a series of recombination experiments using control or diabetic platelets and VLDL, as well as normal or oxidized PL. Basal- and thrombin-stimulated transfers from diabetic VLDL were similar to those from control VLDL. However, LPL- stimulated transfer was decreased when using diabetic VLDL. This was likely due to their lowered ability to be lipolyzed. When we compared the platelets from either diabetic patients or control subjects, we observed that the transfers of PL from control VLDL to diabetic platelets were 20–30% higher than those to control platelets, whether in basal conditions or under LPL or thrombin stimulations. Finally, we observed that, in all conditions tested, the rate of transfers of oxidized PL was two to three times more elevated than that of non oxidized PL. Collective consideration of these data suggests that the transfer of PL from VLDL to platelets might be elevated in type 2 diabetes, favoring oxidative stress-mediated platelet hyperactivation. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: VLDL; Phospholipid transfer; Platelets; Diabetes 1. Introduction Type 2 diabetes is a situation at elevated risk for car- diovascular disease with accelerated rates of atherosclerosis and thrombosis [1]. This may result in part from var- ious lipid disorders including elevated concentrations of Abbreviations: PL, phospholipid; PC, phosphatidylcholine; PE, phos- phatidylethanolamine; [ 14 C]PAPC, 1-palmitoyl-2-[1- 14 C]arachidonyl-PC; cPLA 2 , cytosolic phospholipase A 2 ; TG, triglyceride; LDL, low den- sity lipoprotein; HDL, high density lipoprotein; VLDL, very-low density lipoprotein; LPL, lipoprotein lipase. ∗ Corresponding author. Tel.: +33 4 72 43 81 13; fax: +33 4 72 43 85 24. E-mail address: gabriel.ponsin@insa-lyon.fr (G. Ponsin). triglyceride (TG)-rich very low-density lipoproteins, reduced high-density lipoprotein cholesterol (HDL-C) and a pre- dominance of small dense low-density lipoprotein (LDL) particles [2]. In addition, type 2 diabetes is characterized by platelet hyperactivation [3], even in the absence of any vascu- lar complications [4]. Both dyslipoproteinemia and platelet hyperactivation are likely related to the oxidative stress resulting from hyperglycemia that generates free radicals, glycation and advanced glycation end products [5–7]. While oxidative stress directly contributes to platelet activation, it generates various oxidation products in lipoproteins. Oxida- tion of lipids mainly result in the formation of hydroperoxides in cholesterol esters (CE) and phospholipids (PL) [8]. The 0021-9150/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2008.05.045