title: HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis.
abstract: Patients with HIV are at an increased risk of cardiovascular disease. In this study we investigated the effect of Nef, a secreted HIV protein responsible for the impairment of cholesterol efflux, on the development of atherosclerosis in two animal models. ApoE(-/-) mice fed a high-fat diet and C57BL/6 mice fed a high-fat, high-cholesterol diet were injected with recombinant Nef (40 ng/injection) or vehicle, and the effects of Nef on development of atherosclerosis, inflammation, and dyslipidemia were assessed. In apoE(-/-) mice, Nef significantly increased the size of atherosclerotic lesions and caused vessel remodeling. Nef caused elevation of total cholesterol and triglyceride levels in the plasma while reducing high-density lipoprotein cholesterol levels. These changes were accompanied by a reduction of ABCA1 abundance in the liver, but not in the vessels. In C57BL/6 mice, Nef caused a significant number of lipid-laden macrophages presented in adventitia of the vessels; these cells were absent from the vessels of control mice. Nef caused sharp elevations of plasma triglyceride levels and body weight. Taken together, our findings suggest that Nef causes dyslipidemia and accumulation of cholesterol in macrophages within the vessel wall, supporting the role of Nef in pathogenesis of atherosclerosis in HIV-infected patients.-Cui, H. L., Ditiatkovski, M., Kesani, R., Bobryshev, Y. V., Liu, Y., Geyer, M., Mukhamedova, N., Bukrinsky, M., Sviridov, D. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis.
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia;
authors.forename: Huanhuan L
authors.initials: HL
authors.lastname: Cui
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia;
authors.forename: Michael
authors.initials: M
authors.lastname: Ditiatkovski
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia;
authors.forename: Rajitha
authors.initials: R
authors.lastname: Kesani
authors.affiliation: School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia;
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia;
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Advanced European Studies and Research (CAESAR), Bonn, Germany; and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Geyer
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia;
authors.forename: Nigora
authors.initials: N
authors.lastname: Mukhamedova
authors.affiliation: Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, District of Columbia, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bukrinsky
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; dmitri.sviridov@bakeridi.edu.au.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Sviridov
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D050171:Dyslipidemias / Q000378:metabolism*; D005487:Foam Cells / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006678:HIV / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000097:blood; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D002784:Cholesterol; D006025:Glycosaminoglycans; D054298:Human Immunodeficiency Virus Proteins; D008075:Lipoproteins, HDL; D014280:Triglycerides; D054311:nef Gene Products, Human Immunodeficiency Virus; C577833:Abca1 protein, mouse; C007858:glucuronyl glucosamine glycan sulfate
keywords: HIV; cholesterol; macrophages; metabolic syndrome; reverse cholesterol transport; vessels