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Impact of LDL apheresis on atheroprotective reverse cholesterol transport pathway in familial hypercholesterolemia
Authors:Orsoni Alexina  Villard Elise F  Bruckert Eric  Robillard Paul  Carrie Alain  Bonnefont-Rousselot Dominique  Chapman M John  Dallinga-Thie Geesje M  Le Goff Wilfried  Guerin Maryse
Affiliation:4. ICAN Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié, Paris, France;8. Department of Metabolic Biochemistry, Hôpital de la Pitié, Paris, France;2. Université Pierre et Marie Curie, Paris 6, Paris, France;11. Unit of Molecular and Oncologic Endocrinology, AP-HP, Hôpital de la Pitié-Salpêtrière, Paris, France;112. Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Abstract:
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-β1-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 efflux or to deliver CE to hepatic cells. 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 efflux from macrophages or to deliver CE to hepatic cells.
Keywords:cholesteryl ester transfer protein   low density lipoprotein   high density lipoprotein   cellular cholesterol efflux   high density lipoprotein cholesteryl ester uptake
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