Petra El Khoury1, Wanee Plengpanich2, Eric Frisdal3, Wilfried Le Goff4, Weerapan Khovidhunkit2, Maryse Guerin5. 1. INSERM-UPMC UMR1166, Hôpital de la Pitié, Paris, France; Laboratoire de Biochimie, Faculté de Pharmacie et Pôle Technologie Santé, Université Saint-Joseph, Beirut, Lebanon. 2. Hormonal and Metabolic Disorders Research Unit and Endocrinology and Metabolism Unit, Department of Medecine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Patumwan, Bangkok, Thailand. 3. INSERM-UPMC UMR1166, Hôpital de la Pitié, Paris, France. 4. INSERM-UPMC UMR1166, Hôpital de la Pitié, Paris, France; ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France. 5. INSERM-UPMC UMR1166, Hôpital de la Pitié, Paris, France; ICAN-Institute of CardioMetabolism and Nutrition, Hôpital de la Pitié, Paris, France. Electronic address: maryse.guerin@upmc.fr.
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.
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 humanTHP-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.
Authors: Cécile Low-Kam; David Rhainds; Ken Sin Lo; Amina Barhdadi; Marie Boulé; Sonia Alem; Valérie Pedneault-Gagnon; Eric Rhéaume; Marie-Pierre Dubé; David Busseuil; Robert A Hegele; Guillaume Lettre; Jean-Claude Tardif Journal: J Am Heart Assoc Date: 2018-08-21 Impact factor: 5.501