title: Oxidized LDL Levels Are Increased in HIV Infection and May Drive Monocyte Activation.
abstract: BACKGROUND
  HIV infection is associated with increased cardiovascular risk, and this risk correlates with markers of monocyte activation. We have shown that HIV is associated with a prothrombotic monocyte phenotype, which can be partially mitigated by statin therapy. We therefore explored the relationship between oxidized low-density lipoprotein (oxLDL) particles and monocyte activation.
  
  
  METHODS
  We performed phenotypic analysis of monocytes using flow cytometry on fresh whole blood in 54 patients with HIV and 24 controls without HIV. Plasma levels of oxLDL, soluble CD14, IL-6, and soluble CD163 were measured by enzyme-linked immunosorbent assay. In vitro experiments were performed using flow cytometry.
  
  
  RESULTS
  Plasma levels of oxLDL were significantly increased in HIV infection compared with controls (60.1 units vs. 32.1 units, P < 0.001). Monocyte expression of the oxLDL receptors, CD36 and Toll-like receptor 4, was also increased in HIV. OxLDL levels correlated with markers of monocyte activation, including soluble CD14, tissue factor expression on inflammatory monocytes, and CD36. In vitro stimulation with oxLDL, but not to low-density lipoprotein, resulted in expansion of inflammatory monocytes and increased monocyte expression of tissue factor, recapitulating the monocyte profile we find in HIV disease.
  
  
  CONCLUSIONS
  OxLDL may contribute to monocyte activation, and further study in the context of HIV disease is warranted.
authors: *Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, OH; †Department of Medicine, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH; ‡National Heart, Lung and Blood Institute, Section of Inflammation and Cardiometabolic Diseases, Bethesda, MD; §National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD; ‖Rainbow Babies and Children's Hospital, Cleveland, OH; and ¶Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, Ohio State University, Columbus, OH.
authors: David A
authors: DA
authors: Zidar
authors: Steven
authors: S
authors: Juchnowski
authors: Brian
authors: B
authors: Ferrari
authors: Brian
authors: B
authors: Clagett
authors: Heather A
authors: HA
authors: Pilch-Cooper
authors: Shawn
authors: S
authors: Rose
authors: Benigno
authors: B
authors: Rodriguez
authors: Grace A
authors: GA
authors: McComsey
authors: Scott F
authors: SF
authors: Sieg
authors: Nehal N
authors: NN
authors: Mehta
authors: Michael M
authors: MM
authors: Lederman
authors: Nicholas T
authors: NT
authors: Funderburg
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D055815:Young Adult
chemical_list: D016207:Cytokines; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
references: J Am Coll Cardiol. 2012 Oct 16;60(16):1512-20
references: 22999728
references: Nat Immunol. 2010 Feb;11(2):155-61
references: 20037584
references: AIDS. 2013 Jan 28;27(3):381-9
references: 23079800
references: J Lipid Res. 2000 May;41(5):688-96
references: 10787429
references: Circulation. 2000 Jun 27;101(25):2883-8
references: 10869258
references: Circulation. 2001 Apr 17;103(15):1955-60
references: 11306523
references: Blood. 2002 Jan 1;99(1):199-206
references: 11756172
references: Arthritis Rheum. 2002 Oct;46(10):2578-86
references: 12384915
references: Clin Sci (Lond). 2004 Feb;106(2):215-7
references: 12967321
references: Am J Med. 2004 Mar 15;116(6):420-3
references: 15006592
references: Blood. 1993 Nov 15;82(10):3170-6
references: 7693040
references: J Clin Invest. 1995 Nov;96(5):2322-30
references: 7593619
references: Circulation. 1998 Oct 13;98(15):1487-94
references: 9769301
references: J Infect Dis. 1999 Apr;179(4):859-70
references: 10068581
references: N Engl J Med. 2005 Jan 6;352(1):48-62
references: 15635112
references: AIDS. 2011 Mar 27;25(6):787-95
references: 21412059
references: J Infect Dis. 2011 Oct 15;204(8):1227-36
references: 21917896
references: J Clin Invest. 2012 Feb;122(2):558-68
references: 22214850
references: Clin Infect Dis. 2012 Apr;54(7):984-94
references: 22337823
references: J Acquir Immune Defic Syndr. 2012 Apr 1;59(4):340-6
references: 22156911
references: JAMA. 2012 Jul 25;308(4):379-86
references: 22820791
references: PLoS One. 2012;7(9):e44454
references: 22970224
references: J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):367-71
references: 23507662
references: Nat Immunol. 2013 Aug;14(8):812-20
references: 23812099
references: Adv Immunol. 2013;119:51-83
references: 23886064
references: Int J Cardiol. 2013 Oct 9;168(4):4039-45
references: 23886531
references: Curr Opin HIV AIDS. 2014 Jan;9(1):80-6
references: 24275673
references: Clin Infect Dis. 2014 Feb;58(4):588-95
references: 24253250
references: AIDS. 2014 Mar 27;28(6):831-40
references: 24370480
references: Circulation. 1998 May 12;97(18):1837-47
references: 9603539
references: Nat Rev Cardiol. 2010 Feb;7(2):77-86
references: 20065951
references: J Infect Dis. 2010 Jun 15;201(12):1796-805
references: 20446847
references: HIV Med. 2010 Apr;11(4):225-31
references: 19845792
references: Immunity. 2010 Sep 24;33(3):375-86
references: 20832340
references: J Acquir Immune Defic Syndr. 2010 Nov;55(3):316-22
references: 20581689
references: Eur Heart J. 2011 Jan;32(1):84-92
references: 20943670
references: J Infect Dis. 2011 Mar 15;203(6):780-90
references: 21252259
references: N Engl J Med. 2005 Apr 21;352(16):1685-95
references: 15843671
references: Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1439-45
references: 15860745
references: HIV Clin Trials. 2006 Mar-Apr;7(2):41-7
references: 16798618
references: Curr Opin Lipidol. 2006 Oct;17(5):527-33
references: 16960501
references: J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12
references: 17456578
references: Atherosclerosis. 2008 Jul;199(1):79-86
references: 18054941
references: AIDS Patient Care STDS. 2008 Oct;22(10):771-8
references: 18783326
references: PLoS Med. 2008 Oct 21;5(10):e203
references: 18942885
references: N Engl J Med. 2008 Nov 20;359(21):2195-207
references: 18997196
references: J Acquir Immune Defic Syndr. 2009 Jul 1;51(3):268-73
references: 19387353
references: J Acquir Immune Defic Syndr. 2009 Dec;52(5):553-9
references: 19950429
references: Blood. 2010 Jan 14;115(2):161-7
references: 19828697
references: Blood. 2012 Nov 29;120(23):4599-608
references: 23065151