Impaired serum cholesterol efflux potential is associated with endothelial dysfunction in type 2 diabetic patients

Abstract

Objective: Cellular cholesterol efflux to serum is the first step in reverse cholesterol transport and plays an important role in reducing the accumulation of excess cholesterol in arterial wall and prevents atherosclerosis. This study was performed to investigate whether abnormalities in serum cholesterol efflux potential were related to endothelial dysfunction in type 2 diabetic patients. Methods: 95 type 2 diabetic patients and 19 age-matched healthy controls were recruited. Endothelium-dependent vasodilation (EDVD) and endothelium-independent vasodilation (EIDVD) of the brachial artery were measured by high-resolution vascular ultrasound. Serum cholesterol efflux potential was determined by measuring the transfer of [3 H] cholesterol from SR-BI rich Fu5AH cells to the medium induced by the test serum. Results: Type 2 diabetic patients had significantly lower HDL than controls. Serum cholesterol efflux potential was reduced in diabetic patients (15.0±2.0 vs. 18.5±2.6%, P<0.001), and both EDVD (5.2±2.5 vs. 7.4±3.3%, P=0.001) and EIDVD (13.4±4.5 vs. 15.7±4.2%, P=0.045) were also impaired compared with controls. Serum cholesterol efflux potential correlated with both EDVD (r=0.23, P=0.02) and EIDVD (r=0.24, P=0.02) in diabetic patients. On multiple regression analysis of all subjects (including age, gender, the presence of diabetes, smoking status, body mass index, waist, blood pressure, triglyceride, LDL and serum cholesterol efflux potential), only serum cholesterol efflux potential remained a significant independent determinant of EDVD (r 2 =0.15, P<0.001). Serum cholesterol efflux potential was not an independent determinant of EIDVD. Conclusion: Impaired serum cholesterol efflux potential is related to endothelial dysfunction independent of other cardiovascular risk factors.