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

Abstract

Objectives: CETP 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.

Methods: We 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.

Results: We 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.

Conclusion: HDL 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.

Keywords: CETP; Cholesterol efflux; Genetic deficiency; HDL; Hepatic lipase; Macrophage; Reverse cholesterol transport.