HDL biology
Plasma triglycerides, not LCAT or CETP concentration, drive cholesterol esterification and HDL remodeling (ATVB 1995)
Original title: Triglycerides are major determinants of cholesterol esterification/transfer and HDL remodeling in human plasma
Cholesterol esterification rate and net cholesteryl ester transfer rate were measured in whole plasma from 60 patients with isolated hypercholesterolemia, isolated or mixed hypertriglyceridemia, and 20 normolipidemic controls, alongside LCAT and CETP concentrations by specific immunoassay. Mean esterification and transfer rates were 48% and 73% higher, respectively, in hypertriglyceridemic than normotriglyceridemic subjects, and HDL remodeling during plasma incubation was likewise accelerated. Plasma and VLDL triglyceride levels correlated strongly with esterification rate (r equals .722 and r equals .642), transfer rate (r equals .510 and r equals .491), and HDL remodeling (r equals .625 and r equals .620), while plasma LCAT and CETP concentrations did not differ across groups except for a tendency toward higher CETP in hypercholesterolemic patients (plus 51% in mixed hypertriglyceridemia, plus 20% in hypercholesterolemia). Stepwise regression identified VLDL triglyceride as the sole significant predictor of esterification and transfer rates, indicating triglyceride level, not LCAT or CETP concentration, primarily governs reverse cholesterol transport in plasma.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.