title: Validation of the circulating monocyte being representative of the cholesterol-loaded macrophage: biomediator activity.
abstract: BACKGROUND
  Inflammation is pivotal to atherosclerosis. The monocyte-macrophage, a crucial cell in atherogenesis, is present during all stages of atherosclerosis. However, there is a paucity of data comparing circulating monocytes to cholesterol-laden macrophages (foam cells), with regard to their atherogenic properties, especially in subjects with established risk factors such as hyperlipidemia.
  
  
  OBJECTIVE
  To determine whether the circulating blood monocyte is representative of the cholesterol-loaded macrophage with regard to its proatherogenicity in healthy controls and hyperlipidemic patients.
  
  
  METHODS
  Fasting blood was drawn from 32 subjects (n = 16 controls and n = 16 hyperlipidemic patients), and peripheral blood monocytes were obtained. Also, macrophages were cultured and loaded with acetyl low-density lipoprotein on day 10. Day 1 peripheral blood monocytes and day 11 cholesterol-loaded macrophages were assessed for release of superoxide anion and cytokines (interleukin 1, interleukin 6, tumor necrosis factor alpha); surface expression of CD11b, VLA-4, and CD40; and adhesion to human endothelium.
  
  
  RESULTS
  Monocyte and cholesterol-loaded macrophage superoxide anion release, cytokines, and adhesion of monocytes to human endothelium were significantly increased in hyperlipidemic patients compared with controls. Furthermore, following cholesterol loading, there were no significant differences in monocyte versus cholesterol-loaded macrophage activity (P = .71). Also, CD14 and CD11b surface expression on monocytes was significantly increased in hyperlipidemic patients as compared with controls. The magnitude of change in the monocytes versus cholesterol-loaded macrophages was similar.
  
  
  CONCLUSIONS
  From these studies, we can conclude that the monocyte, which is readily accessible, is an appropriate cell to study for modulation of proatherogenic activity, especially with regard to genomic and proteomic analyses/ microarrays.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, University of California, Davis Medical Center, Sacramento, CA 95817, USA. sridevi.devaraj@ucdmc.ucdavis.edu
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000328:Adult; D039481:CD11b Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005487:Foam Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000096:biosynthesis; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D019013:CD40 Antigens; D016207:Cytokines; C509295:ITGAM protein, human; D039041:Integrin alpha4beta1; D013481:Superoxides
references.citation: J Lipid Res. 2001 Apr;42(4):521-7
references.pmid: 11290823
references.citation: Circulation. 2004 Sep 21;110(12):1564-71
references.pmid: 15364812
references.citation: Atherosclerosis. 1999 Mar;143(1):205-11
references.pmid: 10208497
references.citation: Circulation. 2001 Nov 13;104(20):2395-400
references.pmid: 11705814
references.citation: Metabolism. 1991 Nov;40(11):1119-21
references.pmid: 1943738
references.citation: Nature. 2002 Dec 19-26;420(6917):868-74
references.pmid: 12490960
references.citation: Am J Pathol. 1986 Nov;125(2):284-91
references.pmid: 3024493
references.citation: Arterioscler Thromb. 1993 Jun;13(6):944-50
references.pmid: 8388715
references.citation: Circulation. 2006 May 2;113(17):2135-50; discussion 2150
references.pmid: 16671184
references.citation: J Lipid Res. 1996 Sep;37(9):1978-86
references.pmid: 8895064
references.citation: Circulation. 2000 Jul 11;102(2):191-6
references.pmid: 10889130
references.citation: Nature. 1998 Aug 27;394(6696):894-7
references.pmid: 9732872
references.citation: Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;61(1):19-27
references.pmid: 1683060
references.citation: Atherosclerosis. 1991 Oct;90(2-3):175-81
references.pmid: 1759987
references.citation: J Clin Invest. 1996 Aug 1;98(3):756-63
references.pmid: 8698868
references.citation: Thromb Res. 1993 Aug 1;71(3):237-40
references.pmid: 8211889
references.citation: J Clin Invest. 1998 Jun 15;101(12):2702-10
references.pmid: 9637704