Alterations in the transfer of phospholipids from very-low density lipoproteins to activated platelets in type 2 diabetes.
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 (0.1U/mL) or lipoprotein lipase (LPL, 500ng/mL)-mediated platelet activation. In vitro transfer of radiolabelled PL from VLDL (200microM PL) to platelets (2x10(8)/mL) was measured after incubations of 1h at 37 degrees 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.
Ibrahim
Salam
S
INSERM, U870, IFR62, Lyon F-69008, France.
Guillot
Nicolas
N
Pruneta-Deloche
Valérie
V
Charrière
Sybil
S
Calzada
Catherine
C
Guichardant
Michel
M
Moulin
Philippe
P
Lagarde
Michel
M
Ponsin
Gabriel
G
D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010743:Phospholipids / Q000378:metabolism*; D015539:Platelet Activation; D013696:Temperature; D013917:Thrombin / Q000378:metabolism
D000975:Antioxidants; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D013917:Thrombin; D010100:Oxygen