LDL-apheresis depletes apoE-HDL and pre-β1-HDL in familial hypercholesterolemia: relevance to atheroprotection

Alexina Orsoni,Samir Saheb,Johannes H.M Levels,Geesje Dallinga-Thie,Marielle Atassi,Randa Bittar,Paul Robillard,Eric Bruckert,Anatol Kontush,Alain Carrié,M John Chapman

doi:10.1194/jlr.p016816

Abstract

Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by adsorption, induce selective changes in HDL subpopulations, with relevance to atheroprotection? Five HDL subpopulations were fractionated from pre- and post-LDL-apheresis plasmas of normotriglyceridemic FH subjects (n = 11) on regular LDL-apheresis (>2 years). Apheresis lowered both plasma apoE (-62%) and apoAI (-16%) levels, with preferential, genotype-independent reduction in apoE. The mass ratio of HDL2:HDL3 was lowered from ~1:1 to 0.72:1 by apheresis, reflecting selective removal of HDL2 mass (80% of total HDL adsorbed). Pre-LDL-apheresis, HDL2 subpopulations were markedly enriched in apoE, consistent with ~1 copy of apoE per 4 HDL particles. Large amounts (50-66%) of apoE-HDL were removed by apheresis, preferentially in the HDL2b subfraction (-50%); minor absolute amounts of apoE-HDL were removed from HDL3 subfractions. Furthermore, pre-β1-HDL particle levels were subnormal following removal (-53%) upon apheresis, suggesting that cellular cholesterol efflux may be defective in the immediate postapheresis period. In LDL-receptor (LDL-R) deficiency, LDL-apheresis may enhance flux through the reverse cholesterol transport pathway and equally attenuate potential biglycan-mediated deposition of apoE-HDL in the arterial matrix.

Highlights

Subnormal HDL-cholesterol (HDL-C) and apolipoproteinAI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment
In view of the role of apoE-rich HDL and of pre-␤1-HDL in the reverse cholesterol transport pathway and of the binding of apoE-HDL to arterial matrix biglycans [32,33,34], we evaluated the potential impact of particle adsorption and perturbed metabolism during LDL-apheresis on HDL heterogeneity and on potential HDL-mediated atheroprotection on a background of LDL-receptor (LDL-R) deficiency
The major impact of apheresis on reduction of plasma lipid and apoprotein biomarkers in our FH subjects is entirely consistent with that previously reported by others, and it is largely independent of the nature of the apheresis procedure [25, 28]