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

• Published in: Atherosclerosis 2000-09, Vol.152 (1), p.181-192
• Main Authors: Brites, Fernando D, Bonavita, Carla D, De Geitere, Catherine, Cloës, Marcelo, Delfly, Bernard, Yael, Mario J, Fruchart, Jean-Charles, Wikinski, Regina W, Castro, Graciela R
• Format: Article
• Language: English
• Subjects: Adult; Aged; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biological Transport; Blood and lymphatic vessels; Cardiology. Vascular system; Carrier Proteins - metabolism; Cholesterol - metabolism; Cholesterol efflux; Cholesterol Ester Transfer Proteins; Cholesterol, HDL - blood; Cholesteryl ester transfer protein (CETP); Glycoproteins; High density lipoproteins (HDL); Humans; Hypertriglyceridemia; Hypertriglyceridemia - metabolism; Hypoalphalipoproteinemia; Lecithin:cholesterol acyltransferase (LCAT); Male; Medical sciences; Middle Aged; Phosphatidylcholine-Sterol O-Acyltransferase - metabolism; Probability; Reference Values; Reverse cholesterol transport; Statistics, Nonparametric
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(99)00452-9

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.