HDL biology
Hypertriglyceridemia with low HDL cholesterol raises CETP activity and impairs cellular cholesterol efflux capacity in men (Atherosclerosis 2000)
Original title: Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels
This study compared reverse cholesterol transport pathway steps in men with primary hypertriglyceridemia and low HDL cholesterol versus normotriglyceridemic subjects with or without hypoalphalipoproteinemia. Hypertriglyceridemic patients had decreased apoA-I and apoA-II concentrations, with a selective reduction in LpA-I:A-II particles, elevated apoC-III Lp non-B, and HDL lipid composition showing triglyceride enrichment and cholesterol depletion. Serum-promoted cellular cholesterol efflux, measured using Fu5AH and J774 cell models and confirmed with isolated HDL fractions, was reduced. Lecithin:cholesterol acyltransferase activity tended lower but was not statistically significant, while CETP activity was increased in the hypertriglyceridemic group. The authors conclude that hypertriglyceridemia induces quantitative and qualitative alterations across multiple steps of reverse cholesterol transport, potentially linking it to atherosclerosis.
Original abstract
Hypertriglyceridemia is a complex pathological entity strongly connected to low HDL-C levels but controversially related to the risk of coronary artery disease. In this study, we evaluated the main steps of the antiatherogenic pathway called reverse cholesterol transport in a group of patients with primary hypertriglyceridemia and low HDL-C levels in comparison to normotriglyceridemic subjects with or without hypoalphalipoproteinemia. In patients with primary hypertriglyceridemia, low HDL-C levels were accompanied by decreased apo A-I and apo A-II concentrations. These reductions were manifested 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 showed a triglyceride enrichment and cholesterol depletion. The capacity of serum samples from hypertriglyceridemic patients to promote cellular cholesterol 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. Lecithin:cholesterol acyltransferase (LCAT) activity, the driving force of reverse cholesterol transport, showed a tendency towards lower values in hypertriglyceridemic patients, but this difference was not statistically significant. Additionally, cholesteryl ester transfer protein (CETP) activity was increased in this group of patients. Therefore, hypertriglyceridemia was found to induce quantitative and qualitative alterations in HDL and its subclasses and, consequently, in some steps of reverse cholesterol transport. The abnormalities found in this antiatherogenic pathway and its promoters could constitute a possible connection between hypertriglyceridemia and atherosclerosis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.