title: Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis.
abstract: BACKGROUND
  Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of inflammation, ie, interleukin (IL)-6, are elevated in patients with acute coronary syndromes and may contribute to the exacerbation of atherosclerosis.
  
  
  RESULTS
  To assess the role of IL-6 in atherosclerosis, ApoE-/--IL-6-/- double-knockout mice were generated, fed a normal chow diet, and housed for 53+/-4 weeks. Mortality and blood pressure were unaltered. However, serum cholesterol levels and subsequent atherosclerotic lesion formation (oil red O stain) were significantly increased in ApoE-/--IL-6-/- mice compared with ApoE-/-, wild-type (WT), and IL-6-/- mice. Plaques of ApoE-/--IL-6-/- mice showed significantly reduced transcript and protein levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase (by reverse transcriptase-polymerase chain reaction and immunohistochemistry). Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into the atherosclerotic lesion was significantly reduced in ApoE-/--IL-6-/- mice. The transcript and serum protein (ELISA) levels of IL-10 were significantly reduced.
  
  
  CONCLUSIONS
  Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque formation in ApoEK-/--IL-6-/- mice and leads to maladaptive vascular developmental processes. These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis.
authors.affiliation: Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany. schieffer.bernhard@mh-hannover.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
authors.forename: Tina
authors.initials: T
authors.lastname: Selle
authors.forename: Andres
authors.initials: A
authors.lastname: Hilfiker
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Karsten
authors.initials: K
authors.lastname: Grote
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Maren
authors.initials: M
authors.lastname: Luchtefeld
authors.forename: Christian
authors.initials: C
authors.lastname: Schmittkamp
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure; D003094:Collagen / Q000032:analysis; D006706:Homeostasis; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014657:Vasculitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D003094:Collagen; D020780:Matrix Metalloproteinase 9