Increased Phospholipid Transfer Protein Activity Associated with the Impaired Cellular Cholesterol Efflux in Type 2 Diabetic Subjects with Coronary Artery Disease

Abstract

Reverse cholesterol transport (RCT) is the pathway, by which the excess of cholesterol is removed from peripheral cells to the liver. An early step of RCT is the efflux of free cholesterol from cell membranes that is mediated by high-density lipoproteins (HDL). Phospholipid transfer protein (PLTP) transfers phospholipids between apolipoprotein-B-containing lipoproteins (i.e., chylomicrons and very low-density lipoproteins) and HDL. PLTP contributes to the HDL maturation and increases the ability of HDL to extract the cellular cholesterol. It is known that RCT is impaired in type 2 diabetic patients, especially when cardiovascular complication is associated with. In this study, we measured the serum capacity that promotes cellular cholesterol efflux and the plasma PLTP activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 35), those without CAD (n = 24), and 35 healthy subjects as a sex- and age-matched control. In patients with CAD, plasma triglyceride level was higher compared to controls (p < 0.01) and HDL-cholesterol was lower (p < 0.01 vs control and the patients without CAD). In diabetic patients with or without CAD, PLTP activity was consistently increased, compared to controls, while cellular cholesterol efflux activity was decreased by 20% (p < 0.001) or 13.5% (p < 0.01), respectively. In conclusion, plasma PLTP activity was increased in type 2 diabetic patients with or without CAD, which could impair cellular cholesterol removal and might accelerate atherosclerosis in diabetic patients.