title: Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels.
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.
authors.affiliation: Laboratory of Lipids and Lipoproteins, Department of Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956, Capital Federal, C.P. (1113), Buenos Aires, Argentina. fdbrites@dbc.ffyb.uba.ar
authors.forename: F D
authors.initials: FD
authors.lastname: Brites
authors.forename: C D
authors.initials: CD
authors.lastname: Bonavita
authors.forename: C
authors.initials: C
authors.lastname: De Geitere
authors.forename: M
authors.initials: M
authors.lastname: Cloës
authors.forename: B
authors.initials: B
authors.lastname: Delfly
authors.forename: M J
authors.initials: MJ
authors.lastname: Yael
authors.forename: J
authors.initials: J
authors.lastname: Fruchart
authors.forename: R W
authors.initials: RW
authors.lastname: Wikinski
authors.forename: G R
authors.initials: GR
authors.lastname: Castro
mesh_terms: D000328:Adult; D000368:Aged; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D006023:Glycoproteins; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D011336:Probability; D012016:Reference Values; D018709:Statistics, Nonparametric
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase