Improved plasma cholesterol efflux capacity from human macrophages in patients with hyperalphalipoproteinemia

•Reverse cholesterol transport is improved in patients carrying CETP or LIPC mutations.•Increased HDL3 functionality improves ABCA1-dependent plasma efflux capacity in HALP.•Quantitative elevation in HDL2 in HALP increases SR-BI mediated plasma efflux.•Increased CV risk in CETP or LIPC deficient subject is unrelated to dysfunctional HDL.

ObjectivesCETP or HL deficiencies lead to a marked increase in HDL-C levels however the atheroprotective effect of this phenotype, in particular the ability of HDL particles to remove cholesterol from human macrophages, remains to be determined.MethodsWe measured cholesterol efflux from human THP-1 macrophages to total plasma or to isolated HDL subfractions in patients with HALP carrying molecular defect in either the CETP or LIPC gene.ResultsWe demonstrate that HALP is associated with an increased plasma cholesterol efflux capacity from human macrophages. This observation is primarily related to a stimulation of both SR-BI and ABCA1 dependent efflux pathways as a result of quantitative elevation in HDL2 and enhanced intrinsic capacity of HDL3 subspecies, respectively.ConclusionHDL particles from HALP patients with molecular defect within either CETP or LIPC gene are not dysfunctional and are efficient to stimulate cholesterol efflux from human macrophages.