title: Plasma cholesterol efflux capacity from human THP-1 macrophages is reduced in HIV-infected patients: impact of HAART.
abstract: The capacity of HDL to remove cholesterol from macrophages is inversely associated with the severity of angiographic coronary artery disease. The effect of human immunodeficiency virus (HIV) infection or its treatment on the ability of HDL particles to stimulate cholesterol efflux from human macrophages has never been studied. We evaluated the capacity of whole plasma and isolated HDL particles from HIV-infected subjects (n = 231) and uninfected controls (n = 200), as well as in a subset of 41 HIV subjects receiving highly active antiretroviral therapy (HAART) to mediate cholesterol efflux from human macrophages. Plasma cholesterol efflux capacity was reduced (-12%; P = 0.001) in HIV patients as compared with controls. HIV infection reduced by 27% (P < 0.05) the capacity of HDL subfractions to promote cholesterol efflux from macrophages. We observed a reduced ABCA1-dependent efflux capacity of plasma (-27%; P < 0.0001) from HIV-infected subjects as a result of a reduction in the efflux capacity of HDL3 particles. HAART administration restored the capacity of plasma from HIV patients to stimulate cholesterol efflux from human macrophages (9.4%; P = 0.04). During HIV infection, the capacity of whole plasma to remove cholesterol from macrophages is reduced, thus potentially contributing to the increased coronary heart disease in the HIV population. HAART administration restored the removal of cholesterol from macrophages by increasing HDL functionality.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS1166, Hôpital de la Pitié, Paris, France; Sorbonne Universités, UMPC Univ Paris 6, Paris, France; Université Saint Joseph, Faculté de pharmacie, Beyrouth, Liban.
authors.forename: Petra
authors.initials: P
authors.lastname: El Khoury
authors.affiliation: INSERM, UMRS 1018, CESP, Le Kremlin-Bicêtre, France; Service d'Epidémiologie et de Santé Publique, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin-Bicêtre, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Ghislain
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS1166, Hôpital de la Pitié, Paris, France; Sorbonne Universités, UMPC Univ Paris 6, Paris, France.
authors.forename: Elise F
authors.initials: EF
authors.lastname: Villard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS1166, Hôpital de la Pitié, Paris, France; Sorbonne Universités, UMPC Univ Paris 6, Paris, France; ICAN Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié, Paris, France.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.affiliation: Service de Maladies Infectieuses, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lascoux-Combe
authors.affiliation: Service de Maladies Infectieuses, Hôpital Bichat, AP-HP, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yeni
authors.affiliation: INSERM, UMRS 1018, CESP, Le Kremlin-Bicêtre, France; Service d'Epidémiologie et de Santé Publique, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin-Bicêtre, France; Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: Sorbonne Universités, UMPC Univ Paris 6, Paris, France; ICAN Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Laboratoire de Biologie et Génétique Moléculaires, Paris, France; INSERM UMRS938, Centre de recherche Saint-Antoine, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Vigouroux
authors.affiliation: INSERM, UMRS 1018, CESP, Le Kremlin-Bicêtre, France; Université Paris-Sud, Le Kremlin-Bicêtre, France; Service de Médecine Interne, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS1166, Hôpital de la Pitié, Paris, France; Sorbonne Universités, UMPC Univ Paris 6, Paris, France; ICAN Institute of Cardiometabolism and Nutrition, Hôpital de la Pitié, Paris, France. Electronic address: maryse.guerin@upmc.fr.
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D053440:Lipoproteins, HDL3 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D053440:Lipoproteins, HDL3; D002784:Cholesterol
keywords: antiretroviral therapy; high density lipoprotein function; highly active antiretroviral therapy; human immunodeficiency virus; macrophage cholesterol efflux; reverse cholesterol transport