Abstract-Mean plasma phospholipid transfer protein (PLTP) concentrations were measured for the first time by using a competitive enzyme-linked immunosorbent assay. PLTP mass levels and phospholipid transfer activity values, which were significantly correlated among normolipidemic plasma samples (rϭ0.787, PϽ0.0001), did not differ between normolipidemic subjects (3.95Ϯ1.04 mg/L and 575Ϯ81 nmol ⅐ mL Ϫ1 ⅐ h Ϫ1 , respectively; nϭ30), type IIa hyperlipidemic patients (4.06Ϯ0.84 mg/L and 571Ϯ43 nmol ⅐ mL Ϫ1 ⅐ h Ϫ1 , respectively; nϭ36), and type IIb hyperlipidemic patients (3.90Ϯ0.79 mg/L and 575Ϯ48 nmol ⅐ mL Ϫ1 ⅐ h Ϫ1 , respectively; nϭ33). No significant correlations with plasma lipid parameters were observed among the various study groups. In contrast, plasma concentrations of the related cholesteryl ester transfer protein (CETP) were higher in type IIa and type IIb patients than in normolipidemic controls, and significant, positive correlations with total and low density lipoprotein cholesterol levels were noted. Interestingly, plasma PLTP mass concentration and plasma phospholipid transfer activity were significantly higher in patients with non-insulin-dependent diabetes mellitus (nϭ50) than in normolipidemic controls (6.76Ϯ1.93 versus 3.95Ϯ1.04 mg/L, PϽ0.0001; and 685Ϯ75 versus 575Ϯ81 nmol ⅐ mL, PϽ0.0001, respectively). In contrast, CETP levels did not differ significantly between the 2 groups. Among non-insulin-dependent diabetes mellitus patients, PLTP levels were positively correlated with fasting glycemia and glycohemoglobin levels (rϭ0.341, Pϭ0.0220; and rϭ0.382, Pϭ0.0097, respectively) but not with plasma lipid parameters. It is proposed that plasma PLTP mass levels are related to glucose metabolism rather than to lipid metabolism. Key Words: cholesteryl ester transfer protein Ⅲ lipid transfer Ⅲ ELISA Ⅲ glucose Ⅲ non-insulin-dependent diabetes mellitus I n vivo, plasma lipoproteins do not constitute stable entities but are continuously remodeled through the action of several enzymes and lipid transfer proteins. In particular, cholesteryl ester transfer protein (CETP) 1 and phospholipid transfer protein (PLTP), 2 related proteins belonging to the lipid transfer/lipopolysaccharide binding protein (LT/LBP) family, 1 can promote the exchange of lipid species between various plasma lipoprotein fractions. In fact, studies over the past few years have demonstrated that both CETP and PLTP produce multiple effects on lipoprotein structure and composition. Thus, CETP promotes the exchange of neutral lipids, ie, CEs and triglycerides, between plasma lipoprotein fractions, leading to alterations in both the neutral lipid content and the size distribution of lipoproteins. 2,3 PLTP can facilitate the transfer of phospholipids between lipoprotein particles, 4 and it was lately shown to transfer lipopolysaccharides, 5 unesterified cholesterol, 6 and ␣-tocopherol 7 as well. In addition, PLTP constitutes an important determinant of the size distribution of HDL. 3,8 -12 Taken together, recent advances have raised considerab...

Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by oxidised LDL. Results: Oxidised LDL inhibited endothelium-dependent vasodilation (maximal relaxation [Emax]=58.2± 14.6 vs 99.3±5.2% for incubation without any lipoprotein, p<0.0001). HDL from control subjects significantly reduced the inhibitory effect of oxidised LDL on vasodilatation (Emax=77.6±12.9 vs 59.5±7.7%, p<0.001), whereas HDL from type 2 diabetic patients had no effect (Emax=52.4±20.4 vs 57.2±18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3±2.2 vs 3.1±1.4%, p<0.01) and was highly inversely correlated to Emax for oxidised LDL+HDL in type 2 diabetic patients (r=−0.71, p<0.005). Conclusions/interpretation: In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.

Cholesterol derivatives in oxidized LDL can reduce maximal arterial relaxation through a specific effect on vascular endothelial cells.