TY - JOUR
T1 - Apolipoprotein B-100 and ApoA-II kinetics as determinants of cellular cholesterol efflux
AU - Chan, Dick C.
AU - Hoang, Anh
AU - Barrett, P. Hugh R
AU - Wong, Annett T Y
AU - Nestel, Paul John
AU - Sviridov, Dmitri
AU - Watts, Gerald F
PY - 2012/9
Y1 - 2012/9
N2 - Context: Cellular cholesterol efflux is a key step in reverse cholesterol transport and may depend on the metabolism of apolipoprotein (apo) B-100, apoA-I ,and apoA-II. Objective: We examined the associations between cholesterol efflux and plasma concentrations and kinetics of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL)-apoB-100, high-density lipoprotein (HDL)-apoA-I, and HDL-apoA-II in men. Design, Subjects, and Methods: Thirty men were recruited from the community with a wide range of body mass index. The capacity of plasma and HDL to efflux cholesterol was measured ex vivo. Apolipoprotein kinetics were measured using stable isotope techniques and multicompartmental modeling. Results: Cholesterol efflux to whole plasma was correlated with plasma levels of cholesterol, triglyceride, apoB-100, insulin, cholesteryl ester transfer protein, and lecithin-cholesterol acyltransferase, body mass index and waist circumference (P < 0.05 in all). Cholesterol efflux was inversely correlated with the fractional catabolic rate (FCR) of VLDL (r = -0.728), IDL (r = -0.662), and LDL-apoB-100 (r = -0.479) but positively correlated with the FCR (r = 0.438) and production rate (r = 0.468) of HDL-apoA-II. In multiple regression analysis, the concentration and FCR of VLDL-apoB-100 (β-coefficient = 0.708 and -0.518, respectively) and IDL-apoB-100 (β-coefficient = 0.354 and -0.447, respectively) were independent predictors of cholesterol efflux. The association of cholesterol efflux with apoB-100 metabolism was diminished after removal of apoB-100-containing lipoproteins from plasma prior to efflux. All associations, except for cholesteryl ester transfer protein, were lost when cholesterol efflux to isolated HDL was tested. Conclusions: The plasma concentration and kinetics of apoB-100-containing lipoproteins are significant predictors of the capacity of whole plasma to effect cellular cholesterol efflux.
AB - Context: Cellular cholesterol efflux is a key step in reverse cholesterol transport and may depend on the metabolism of apolipoprotein (apo) B-100, apoA-I ,and apoA-II. Objective: We examined the associations between cholesterol efflux and plasma concentrations and kinetics of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL)-apoB-100, high-density lipoprotein (HDL)-apoA-I, and HDL-apoA-II in men. Design, Subjects, and Methods: Thirty men were recruited from the community with a wide range of body mass index. The capacity of plasma and HDL to efflux cholesterol was measured ex vivo. Apolipoprotein kinetics were measured using stable isotope techniques and multicompartmental modeling. Results: Cholesterol efflux to whole plasma was correlated with plasma levels of cholesterol, triglyceride, apoB-100, insulin, cholesteryl ester transfer protein, and lecithin-cholesterol acyltransferase, body mass index and waist circumference (P < 0.05 in all). Cholesterol efflux was inversely correlated with the fractional catabolic rate (FCR) of VLDL (r = -0.728), IDL (r = -0.662), and LDL-apoB-100 (r = -0.479) but positively correlated with the FCR (r = 0.438) and production rate (r = 0.468) of HDL-apoA-II. In multiple regression analysis, the concentration and FCR of VLDL-apoB-100 (β-coefficient = 0.708 and -0.518, respectively) and IDL-apoB-100 (β-coefficient = 0.354 and -0.447, respectively) were independent predictors of cholesterol efflux. The association of cholesterol efflux with apoB-100 metabolism was diminished after removal of apoB-100-containing lipoproteins from plasma prior to efflux. All associations, except for cholesteryl ester transfer protein, were lost when cholesterol efflux to isolated HDL was tested. Conclusions: The plasma concentration and kinetics of apoB-100-containing lipoproteins are significant predictors of the capacity of whole plasma to effect cellular cholesterol efflux.
UR - http://www.scopus.com/inward/record.url?scp=84866145899&partnerID=8YFLogxK
U2 - 10.1210/jc.2012-1522
DO - 10.1210/jc.2012-1522
M3 - Article
C2 - 22745238
AN - SCOPUS:84866145899
VL - 97
JO - The Journal of Clinical Endocrinology and Metabolism
JF - The Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 9
ER -
