Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis.
Arterioscler Thromb Vasc Biol
; 29(4): 525-31, 2009 Apr.
Article
en En
| MEDLINE
| ID: mdl-19164812
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. METHODS ANDRESULTS:
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Aterosclerosis
/
Factores de Transcripción STAT
/
Proteínas Supresoras de la Señalización de Citocinas
/
Quinasas Janus
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
España