title: Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis.
abstract: OBJECTIVE
  Suppressors of cytokine signaling (SOCS) proteins are intracellular regulators of receptor signal transduction, mainly Janus kinase/signal transducers and activators of transcription (JAK/STAT). We investigated the effects of SOCS modulation on the JAK/STAT-dependent responses in vascular cells, and their implication in atherosclerotic plaque development.
  
  
  RESULTS
  Immunohistochemistry in human plaques revealed a high expression of SOCS1 and SOCS3 by vascular smooth muscle cells (VSMCs) and macrophages in the inflammatory region of the shoulders, when compared to the fibrous area. SOCS were also increased in aortic lesions from apoE(-/-) mice. In cultured VSMCs, endothelial cells, and monocytes, SOCS1 and SOCS3 were transiently induced by proinflammatory cytokines, proatherogenic lipoproteins, and immune molecules. Furthermore, overexpression of SOCS suppressed STAT activation and reduced inflammatory gene expression and cell growth, whereas SOCS knockdown increased these cell responses. In vivo, antisense oligodeoxynucleotides targeting SOCS3 exacerbated the atherosclerotic process in apoE(-/-) mice by increasing the size, leukocyte content, and chemokine expression in the lesions.
  
  
  CONCLUSIONS
  SOCS expressed in atherosclerotic lesions are key regulators of vascular cell responses. Activation of this endogenous antiinflammatory pathway might be of interest in the treatment of atherosclerosis.
authors.affiliation: Renal and Vascular Inflammation Lab, Fundacion Jimenez Diaz, Autonoma University, Madrid, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ortiz-Muñoz
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Martin-Ventura
authors.forename: Purificacion
authors.initials: P
authors.lastname: Hernandez-Vargas
authors.forename: Beñat
authors.initials: B
authors.lastname: Mallavia
authors.forename: Virginia
authors.initials: V
authors.lastname: Lopez-Parra
authors.forename: Oscar
authors.initials: O
authors.lastname: Lopez-Franco
authors.forename: Begoña
authors.initials: B
authors.lastname: Muñoz-Garcia
authors.forename: Paula
authors.initials: P
authors.lastname: Fernandez-Vizarra
authors.forename: Luis
authors.initials: L
authors.lastname: Ortega
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.forename: Carmen
authors.initials: C
authors.lastname: Gomez-Guerrero
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology; D002339:Carotid Arteries / Q000201:enzymology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D010766:Phosphorylation; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D053612:Janus Kinases