title: Role of suppressor of cytokine signaling-1 in murine atherosclerosis.
abstract: BACKGROUND
  While the impact of inflammation as the substantial driving force of atherosclerosis has been investigated in detail throughout the years, the influence of negative regulators of pro-atherogenic pathways on plaque development has remained largely unknown. Suppressor of cytokine signaling (SOCS)-1 potently restricts transduction of various inflammatory signals and, thereby modulates T-cell development, macrophage activation and dendritic cell maturation. Its role in atherogenesis, however has not been elucidated so far.
  
  
  RESULTS
  Loss of SOCS-1 in the low-density lipoprotein receptor deficient murine model of atherosclerosis resulted in a complex, systemic and ultimately lethal inflammation with increased generation of Ly-6C(hi) monocytes and activated macrophages. Even short-term exposure of these mice to high-cholesterol dieting caused enhanced atherosclerotic plaque development with accumulation of M1 macrophages, Ly-6C positive cells and neutrophils.
  
  
  CONCLUSIONS
  Our data not only imply that SOCS-1 is athero-protective but also emphasize the fundamental, regulatory importance of SOCS-1 in inflammation-prone organisms.
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Grothusen
authors.forename: Harald
authors.initials: H
authors.lastname: Schuett
authors.forename: Anja
authors.initials: A
authors.lastname: Hillmer
authors.forename: Stefan
authors.initials: S
authors.lastname: Lumpe
authors.forename: Karsten
authors.initials: K
authors.lastname: Grote
authors.forename: Matthias
authors.initials: M
authors.lastname: Ballmaier
authors.forename: Andre
authors.initials: A
authors.lastname: Bleich
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
authors.forename: Maren
authors.initials: M
authors.lastname: Luchtefeld
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology; D059305:Diet, High-Fat; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011973:Receptors, LDL / Q000502:physiology*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; D004268:DNA-Binding Proteins; C494192:Ly-6C antigen, mouse; C499308:Rag2 protein, mouse; D011973:Receptors, LDL; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins