title: Triglycerides are major determinants of cholesterol esterification/transfer and HDL remodeling in human plasma.
abstract: Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are responsible for the esterification of cell-derived cholesterol and for the transfer of newly synthesized cholesteryl esters (CE) from HDL to apoB-containing lipoproteins in human plasma. LCAT and CETP are also crucial factors in HDL remodeling, a process by which HDL particles with a high capacity for cell cholesterol uptake are generated in plasma. In the present study, cholesterol esterification and transfer were evaluated in 60 patients with isolated hypercholesterolemia (HC, n = 20) and isolated (HTG, n = 20) or mixed hypertriglyceridemia (MHTG, n = 20) and in 20 normolipidemic healthy individuals (NL). Cholesterol esterification rate (CER) and net CE transfer rate (CETR) were measured in whole plasma. LCAT and CETP concentrations were determined by specific immunoassays. HDL remodeling was analyzed by monitoring changes in HDL particle size distribution during incubation of whole plasma at 37 degrees C. Mean CER and CETR were 48% and 73% higher, respectively, in hypertriglyceridemic (HTG + MHTG) versus normotriglyceridemic individuals. HDL remodeling was also significantly accelerated in plasma from hypertriglyceridemic patients. Strong positive correlations were found in the total sample between plasma and VLDL triglyceride levels and CER (r = .722 and r = .642, respectively), CETR (r = .510 and r = .491, respectively), and HDL remodeling (r = .625 and r = .620, respectively). No differences in plasma LCAT and CETP concentrations were found among the various groups except for a tendency toward higher CETP levels in hypercholesterolemic patients (+51% in MHTG and +20% in HC) versus control subjects (NL). By stepwise regression analysis, VLDL triglyceride level was the sole significant predictor of CER and CETR and contributed significantly together with baseline HDL particle distribution to HDL remodeling. These results indicate that plasma triglyceride level is a major factor in the regulation of cholesterol esterification/transfer and HDL remodeling in human plasma, whereas LCAT/CETP concentrations play a minor role in the modulation of reverse cholesterol transport.
authors.affiliation: Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: S
authors.initials: S
authors.lastname: Michelagnoli
authors.forename: R
authors.initials: R
authors.lastname: Longhi
authors.forename: G
authors.initials: G
authors.lastname: Gianfranceschi
authors.forename: F
authors.initials: F
authors.lastname: Pazzucconi
authors.forename: L
authors.initials: L
authors.lastname: Calabresi
authors.forename: C R
authors.initials: CR
authors.lastname: Sirtori
authors.forename: G
authors.initials: G
authors.lastname: Franceschini
mesh_terms: D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D006023:Glycoproteins; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D014280:Triglycerides / Q000097:blood*
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D014280:Triglycerides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase