title: Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice.
abstract: BACKGROUND
  Lipopolysaccharide (LPS), which is released from gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated the effect of endogenous apoCI expression on LPS-induced atherosclerosis in mice.
  
  
  RESULTS
  Twelve-week-old apoe-/- apoc1-/- and apoe-/- apoc1+/+ mice received weekly intraperitoneal injections of LPS (50 microg) or vehicle for a period of 10 weeks, and atherosclerosis development was assessed in the aortic root. LPS administration did not affect atherosclerotic lesion area in apoe-/- apoc1-/- mice but increased it in apoe-/- apoc1+/+ mice. In fact, apoCI expression increased the LPS-induced atherosclerotic lesion area by 60% (P<0.05), concomitant with an increase in LPS-induced plasma levels of fibrinogen and E-selectin. This indicated that apoCI increased the LPS-induced inflammatory state, both systemically (ie, fibrinogen) and at the level of the vessel wall (ie, E-selectin). In addition, both macrophage-derived apoCI and HDL-associated apoCI increased the LPS-induced tumor necrosis factor-alpha response by macrophages in vitro.
  
  
  CONCLUSIONS
  We conclude that apoCI is crucially involved in LPS-induced atherosclerosis in apoe-/- mice, which mainly relates to an increased inflammatory response toward LPS. We anticipate that apoCI plasma levels contribute to accelerated atherosclerosis development in individuals who have chronic infection.
authors.affiliation: The Netherlands Organization for Applied Scientific Research-Quality of Life, Department of Biomedical Research, Gaubius Laboratory, Leiden, The Netherlands. M.Westerterp@lumc.nl
authors.forename: Marit
authors.initials: M
authors.lastname: Westerterp
authors.forename: Jimmy F P
authors.initials: JF
authors.lastname: Berbée
authors.forename: Nuno M M
authors.initials: NM
authors.lastname: Pires
authors.forename: Geertje J D
authors.initials: GJ
authors.lastname: van Mierlo
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
mesh_terms: D000818:Animals; D001056:Apolipoproteins C / Q000235:genetics* / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood; D019040:E-Selectin / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006937:Hypercholesterolemia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014657:Vasculitis / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D001056:Apolipoproteins C; D015415:Biomarkers; D008076:Cholesterol, HDL; D019040:E-Selectin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen