TY - JOUR
T1 - Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia
AU - Orsoni, Alexina
AU - Villard, Elise F.
AU - Bruckert, Eric
AU - Robillard, Paul
AU - Carrie, Alain
AU - Bonnefont-Rousselot, Dominique
AU - Chapman, M. John
AU - Dallinga-Thie, Geesje M.
AU - Le Goff, Wilfried
AU - Guerin, Maryse
PY - 2012
Y1 - 2012
N2 - In familial hypercholesterolemia (FH), low HDL cholesterol (HDL-C) levels are associated with functional alterations of HDL particles that reduce their capacity to mediate the reverse cholesterol transport (RCT) pathway. The objective of this study was to evaluate the consequences of LDL apheresis on the efficacy of the RCT pathway in FH patients. LDL apheresis markedly reduced abnormal accelerated cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer from HDL to LDL, thus reducing their CE content. Equally, we observed a major decrease (-53%; P <0.0001) in pre-beta 1-HDL levels. The capacity of whole plasma to mediate free cholesterol efflux from human macrophages was reduced (-15%; P <0.02) following LDL apheresis. Such reduction resulted from a marked decrease in the ABCA1-dependent efflux (-71%; P <0.0001) in the scavenger receptor class B type I-dependent efflux (-21%; P <0.0001) and in the ABCG1-dependent pathway (-15%; P <0.04). However, HDL particles isolated from FH patients before and after LDL apheresis displayed a similar capacity to mediate cellular free cholesterol effl ux or to deliver CE to hepatic cells.(jlr) We demonstrate that rapid removal of circulating lipoprotein particles by LDL apheresis transitorily reduces RCT. However, LDL apheresis is without impact on the intrinsic ability of HDL particles to promote either cellular free cholesterol effl ux from macrophages or to deliver CE to hepatic cells.-Orsoni, A., E. F. Villard, E. Bruckert, P. Robillard, A. Carrie, D. Bonnefont-Rousselot, M. J. Chapman, G. M. Dallinga-Thie, W. Le Goff, and M. Guerin. Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia. J. Lipid Res. 2012. 53: 767-775
AB - In familial hypercholesterolemia (FH), low HDL cholesterol (HDL-C) levels are associated with functional alterations of HDL particles that reduce their capacity to mediate the reverse cholesterol transport (RCT) pathway. The objective of this study was to evaluate the consequences of LDL apheresis on the efficacy of the RCT pathway in FH patients. LDL apheresis markedly reduced abnormal accelerated cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester (CE) transfer from HDL to LDL, thus reducing their CE content. Equally, we observed a major decrease (-53%; P <0.0001) in pre-beta 1-HDL levels. The capacity of whole plasma to mediate free cholesterol efflux from human macrophages was reduced (-15%; P <0.02) following LDL apheresis. Such reduction resulted from a marked decrease in the ABCA1-dependent efflux (-71%; P <0.0001) in the scavenger receptor class B type I-dependent efflux (-21%; P <0.0001) and in the ABCG1-dependent pathway (-15%; P <0.04). However, HDL particles isolated from FH patients before and after LDL apheresis displayed a similar capacity to mediate cellular free cholesterol effl ux or to deliver CE to hepatic cells.(jlr) We demonstrate that rapid removal of circulating lipoprotein particles by LDL apheresis transitorily reduces RCT. However, LDL apheresis is without impact on the intrinsic ability of HDL particles to promote either cellular free cholesterol effl ux from macrophages or to deliver CE to hepatic cells.-Orsoni, A., E. F. Villard, E. Bruckert, P. Robillard, A. Carrie, D. Bonnefont-Rousselot, M. J. Chapman, G. M. Dallinga-Thie, W. Le Goff, and M. Guerin. Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia. J. Lipid Res. 2012. 53: 767-775
U2 - https://doi.org/10.1194/jlr.M024141
DO - https://doi.org/10.1194/jlr.M024141
M3 - Article
C2 - 22338009
SN - 0022-2275
VL - 53
SP - 767
EP - 775
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 4
ER -