title: Monocyte activation from interferon-α in HIV infection increases acetylated LDL uptake and ROS production.
abstract: Atherosclerosis is an inflammatory disease that is accelerated in human immunodeficiency virus (HIV) infection. Individuals with HIV infection have an activated type I interferon (IFN) monocyte phenotype, which may enhance uptake of modified low-density lipoprotein (LDL) thereby initiating a prefoam cell pathology and recruitment into atherosclerotic plaques. In a sampling of HIV-infected subjects, an increase in monocyte activation genes, MX1 and CXCL10, correlated with monocyte expression of the scavenger receptor A (SR-A), a major receptor for lipid uptake and foam cell formation. Monocytes from HIV-infected subjects accumulated more lipid than control uninfected subjects. We modeled increased activation in HIV infection by priming human monocytes with IFNα followed by exposure to acetylated LDL (acLDL). Exposure to IFNα increased acLDL uptake, which generated increased cellular reactive oxygen species (ROS). We posit that HIV infection augments formation of arterial plaques by triggering monocyte activation with a type I IFN profile, which induces SR-A expression, lipid uptake, and subsequent ROS production. These findings may explain in part why HIV-infected individuals with chronic immune activation have an increased risk of atherosclerosis.
authors.affiliation: 1 Department of Laboratory Medicine, San Francisco Veterans Affairs Medical Center, University of California , San Francisco, California.
authors.forename: Lynn
authors.initials: L
authors.lastname: Pulliam
authors.forename: Cyrus
authors.initials: C
authors.lastname: Calosing
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.forename: Hans
authors.initials: H
authors.lastname: Rempel
mesh_terms: D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D005487:Foam Cells / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012306:Risk; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D054357:Chemokine CXCL10; D016898:Interferon-alpha; D008077:Lipoproteins, LDL; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D017382:Reactive Oxygen Species; D051117:Scavenger Receptors, Class A; C032629:acetyl-LDL
references.citation: AIDS. 2009 Jun 1;23(9):1059-67
references.pmid: 19390417
references.citation: Cell Metab. 2010 Aug 4;12(2):142-53
references.pmid: 20674859
references.citation: Trends Cardiovasc Med. 2014 Jan;24(1):45-51
references.pmid: 23916809
references.citation: HIV Clin Trials. 2006 Mar-Apr;7(2):41-7
references.pmid: 16798618
references.citation: Chem Phys Lipids. 2011 Sep;164(6):479-87
references.pmid: 21683693
references.citation: J Infect Dis. 2011 Dec 15;204(12):1927-35
references.pmid: 22006994
references.citation: Ann Med. 2010 Sep;42(6):394-403
references.pmid: 20568979
references.citation: J Am Coll Cardiol. 2013 Feb 5;61(5):511-23
references.pmid: 23369416
references.citation: Cytometry A. 2010 Mar;77(3):231-42
references.pmid: 20014301
references.citation: J Biol Chem. 2000 Apr 28;275(17):12633-8
references.pmid: 10777555
references.citation: Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):461-71
references.pmid: 10073945
references.citation: J Clin Endocrinol Metab. 1992 May;74(5):1045-52
references.pmid: 1373735
references.citation: Thromb Haemost. 2010 Aug;104(2):191-3
references.pmid: 20431844
references.citation: Antioxid Redox Signal. 2012 Dec 15;17(12):1785-95
references.pmid: 22540532
references.citation: Am J Med Sci. 2011 Aug;342(2):135-42
references.pmid: 21747278
references.citation: AIDS. 2010 Jun 19;24(10):1415-23
references.pmid: 20495440
references.citation: PLoS One. 2012;7(5):e37000
references.pmid: 22606325
references.citation: Science. 2013 Apr 12;340(6129):207-11
references.pmid: 23580529
references.citation: AIDS. 2012 Nov 28;26(18):2409-12
references.pmid: 23032411
references.citation: J Infect Dis. 2011 Oct 15;204(8):1227-36
references.pmid: 21917896
references.citation: Arthritis Rheum. 2011 Feb;63(2):492-502
references.pmid: 21280004
references.citation: Science. 2013 Apr 12;340(6129):202-7
references.pmid: 23580528
references.citation: J Neuroimmunol. 2004 Dec;157(1-2):93-8
references.pmid: 15579285
references.citation: J Acquir Immune Defic Syndr. 2012 Aug 1;60(4):359-68
references.pmid: 22592585
references.citation: AIDS. 2009 Sep 10;23(14):1841-9
references.pmid: 19455012
references.citation: J Acquir Immune Defic Syndr. 2005 Mar 1;38(3):310-3
references.pmid: 15735450
references.citation: Antivir Ther. 2012;17(4):755-61
references.pmid: 22301072
references.citation: Clin Dev Immunol. 2012;2012:534929
references.pmid: 22203858
references.citation: AIDS. 2011 Nov 13;25(17):2133-42
references.pmid: 21857489
references.citation: Amino Acids. 2003 Dec;25(3-4):283-92
references.pmid: 14661091
references.citation: J Clin Invest. 2003 Feb;111(3):389-97
references.pmid: 12569165
references.citation: Circulation. 2008 Jul 8;118(2):198-210
references.pmid: 18566320
references.citation: Clin Chim Acta. 2013 Sep 23;424:245-52
references.pmid: 23782937
references.citation: BMC Immunol. 2011 Jul 07;12:37
references.pmid: 21736734
references.citation: J Exp Med. 2006 Nov 27;203(12):2613-25
references.pmid: 17101731
references.citation: Circ Res. 2009 Apr 24;104(8):952-60
references.pmid: 19265037
references.citation: AIDS. 2011 Aug 24;25(13):1637-46
references.pmid: 21646903
references.citation: AIDS. 2011 Sep 10;25(14):1721-6
references.pmid: 21750421
references.citation: Blood. 2007 Oct 15;110(8):2907-15
references.pmid: 17638846
references.citation: J Infect Dis. 2012 Jun;205 Suppl 3:S368-74
references.pmid: 22577210
references.citation: Circulation. 2001 Nov 27;104(22):2673-8
references.pmid: 11723017
references.citation: AIDS. 2012 Apr 24;26(7):843-53
references.pmid: 22313961
references.citation: Arthritis Rheum. 2012 Sep;64(9):2975-85
references.pmid: 22549550
references.citation: J Leukoc Biol. 2010 Apr;87(4):589-98
references.pmid: 19952353
references.citation: J Infect Dis. 2013 Feb 15;207(4):628-37
references.pmid: 23204179
references.citation: J Infect Dis. 2012 Jun;205 Suppl 3:S375-82
references.pmid: 22577211
references.citation: AIDS. 2002 Feb 15;16(3):353-8
references.pmid: 11834946