Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels

Hypertriglyceridemia is a complex pathological entity strongly connected to low HDL-C levels but controversially related to the risk of coronary arter y disease. In this study, we evaluated the main steps of the antiatherogeni c pathway called reverse cholesterol transport in a group of patients with primary hypertriglyceridemia and low HDL-C levels in comparison to normotri glyceridemic subjects with or without hypoalphalipoproteinemia. In patients with primary hypertriglyceridemia, low HDL-C levels were accompanied by de creased apo A-I and apo A-II concentrations. These reductions were manifest ed by a selective reduction in LpA-I:A-II particles. In addition, apo C-III Lp non B was found to be elevated and HDL lipid percentage composition sho wed a triglyceride enrichment and cholesterol depletion. The capacity of se rum samples from hypertriglyceridemic patients to promote cellular choleste rol efflux was reduced, as evidenced by using two different cellular models , Fu5AH and J774 cells. This impaired cholesterol efflux promotion was also corroborated by incubations of isolated HDL fractions with Fu5AH cells. Le cithin:cholesterol acyltransferase (LCAT) activity, the driving force of re verse cholesterol transport, showed a tendency towards lower values in hype rtriglyceridemic patients, but this difference was not statistically signif icant. Additionally, cholesteryl ester transfer protein (CETP) activity was increased in this group of patients. Therefore, hypertriglyceridemia was f ound to induce quantitative and qualitative alterations in HDL and its subc lasses and, consequently, in some steps of reverse cholesterol transport. T he abnormalities found in this antiatherogenic pathway and its promoters co uld constitute a possible connection between hypertriglyceridemia and ather osclerosis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.