Cellular cholesterol efflux and cholesterol loading capacity of serum: effects of LDL-apheresis

M.P Adorni,F Zimetti,M Puntoni,F Bigazzi,F Sbrana,F Minichilli,F Bernini,N Ronda,E Favari,T Sampietro

doi:10.1194/jlr.p024810

Abstract

High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to reduce LDL-C levels, has been shown to also affect HDL levels and composition. We studied LDL-apheresis effects on six FH and nine FCH subjects' serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. The procedure reduced total cholesterol (TC), LDL-C, and apoB plasma levels (-69%, -80% and -74%, respectively), parameters only partially restored two days later. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (-27% and -16%, respectively), were restored to almost normal levels two days later. LDL-apheresis reduced serum aqueous diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored whereas ABCA1-CEC remained low two days later. Sera immediately and two days after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion, LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces also serum capacity to deliver cholesterol to macrophages. Despite a potentially negative effect on HDL levels and composition, LDL-apheresis may counteract foam cells formation.

Highlights

High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH)
HDL-C and apoA-I plasma levels were reduced by LDL-apheresis [Ϫ27% (P < 0.001) and Ϫ16% (P < 0.01), respectively]; two days later, plasma HDL-C and apoA-I levels had returned to concentrations similar to those detected before the procedure [Ϫ11% and Ϫ1%, respectively; not significant (NS)]
TG levels were markedly reduced after LDL-apheresis (Ϫ63%; P < 0.01); two days later, the TG plasma levels increased to about 80% of preprocedure values (NS)

Summary

Introduction

High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). We studied LDL-apheresis effects on six FH and nine FCH subjects’ serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (؊27% and ؊16%, respectively), were restored to almost normal levels two days later. Cellular cholesterol efflux and cholesterol loading capacity of serum: effects of LDL-apheresis. Pre-␤ (lipid free/poor apoA-I) HDL particles are acceptors for the ATP-binding cassette A1 (ABCA1)-mediated cholesterol unidirectional efflux [6, 7], whereas mature HDL are involved in aqueous diffusion (AD) and scavenger receptor BI (SR-BI)-mediated efflux, Familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) are common inherited disor-.

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Conclusion