Disturbances of the transfer of cholesterol to high-density lipoprotein (HDL) in patients with peripheral artery disease with or without type 2 diabetes mellitus

Introduction: Low high-density lipoprotein (HDL)-cholesterol is frequent in patients with peripheral artery disease (PAD) and also in type 2 diabetes mellitus (T2DM), the major risk factor for PAD. The transfer of cholesterol from the other lipoproteins to HDL is an important aspect of HDL metabolism and function, and may contribute to atherogenic mechanisms that lead to PAD development. Objective: The aim of this study was to investigate the status of cholesterol transfers in patients with PAD without or with T2DM. Methods: Patients with PAD (n = 19), with PAD and T2DM (PAD + DM, n = 19), and healthy controls (n = 20), all paired for age, gender, and BMI were studied. Transfer of both forms of cholesterol, unesterified (UC) and esterified (EC), was performed by incubating plasma with a donor nanoemulsion containing radioactive UC and EC, followed by chemical precipitation and HDL radioactive counting. Results: Low-density lipoprotein (LDL)-cholesterol and triglycerides were similar in the three groups. Compared to controls, HDL-C was lower in PAD + DM (p < 0.05), but not in PAD. Transfer of UC was lower in PAD + DM than in PAD and controls (4.18 +/- 1.17%, 5.13 +/- 1.44%, 6.59 +/- 1.25%, respectively, p < 0.001). EC transfer tended to be lower in PAD + DM than in controls (2.96 +/- 0.60 vs 4.12 +/- 0.89%, p = 0.05). Concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), both involved in HDL metabolism, were not different among the three groups. Conclusion: Deficient cholesterol transfer to HDL may play a role in PAD pathogenesis. Since UC transfer to HDL was lower in PAD + DM compared to PAD alone, it is possible that defective HDL metabolism may contribute to the higher PAD incidence in patients with T2DM.Keywords