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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Published on: January 22, 2019

Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis

Guadalupe Ortiz-Muñoz1, Jose Luis Martin-Ventura, Purificacion Hernandez-Vargas

  • 1Renal and Vascular Inflammation Lab, Fundacion Jimenez Diaz, Autonoma University, Madrid, Spain.

Arteriosclerosis, Thrombosis, and Vascular Biology
|January 24, 2009
PubMed
Abstract

Insights

Suppressors of cytokine signaling (SOCS) proteins regulate vascular cell responses in atherosclerosis. Modulating SOCS impacts plaque development, suggesting potential therapeutic strategies for this inflammatory disease.

Area of Science:

  • Vascular Biology
  • Immunology
  • Cardiovascular Research

Background:

  • Suppressors of cytokine signaling (SOCS) proteins are key intracellular regulators of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways.
  • SOCS proteins play a critical role in modulating cellular responses to inflammatory and growth signals.

Purpose of the Study:

  • To investigate the role of SOCS modulation in vascular cells.
  • To determine the implication of SOCS in the development of atherosclerotic plaques.

Main Methods:

  • Immunohistochemistry on human atherosclerotic plaques and murine aortic lesions.
  • In vitro studies using cultured vascular smooth muscle cells, endothelial cells, and monocytes.
  • In vivo experiments using apoE(-/-) mice treated with antisense oligodeoxynucleotides targeting SOCS3.

Main Results:

  • High expression of SOCS1 and SOCS3 was observed in macrophages and vascular smooth muscle cells within human atherosclerotic plaques.
  • SOCS1 and SOCS3 were induced by pro-inflammatory stimuli in vascular cells.
  • Overexpression of SOCS suppressed STAT activation and inflammatory gene expression, while SOCS knockdown enhanced these responses.
  • In vivo, SOCS3 inhibition exacerbated atherosclerosis in apoE(-/-) mice.

Conclusions:

  • SOCS proteins are crucial regulators of vascular cell responses within atherosclerotic lesions.
  • The endogenous anti-inflammatory pathway involving SOCS presents a potential therapeutic target for atherosclerosis treatment.

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