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Title: Gene delivery of suppressors of cytokine signaling (SOCS) inhibits inflammation and atherosclerosis development in mice
Authors: Recio Cruz, Carlota Pilar 
Oguiza, Ainhoa
Mallavia, Beñat
Lazaro, Iolanda
Ortiz-Muñoz, Guadalupe
Lopez-Franco, Oscar
Egido, Jesus
Gomez-Guerrero, Carmen
UNESCO Clasification: 3207 Patología
Keywords: SOCS
Inflammation, et al
Issue Date: 2015
Project: SAF2012-38830
FIS PI10/00072
Journal: Basic Research in Cardiology 
Abstract: Chronic activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway contributes to vascular inflammation and atherosclerosis by inducing expression of genes involved in cell proliferation, differentiation and migration. We aimed to investigate whether enforced expression of negative regulators, the suppressors of cytokine signaling (SOCS1 and SOCS3), inhibits harmful JAK/STAT-mediated responses and affects atherosclerosis in apolipoprotein E knockout mice. Adenovirus-mediated SOCS1 transgene expression impaired the onset and progression of atherosclerosis without impact on lipid profile, whereas SOCS3 was only effective on early atherosclerosis. Mechanistically, SOCS gene delivery, primarily SOCS1, attenuated STAT1 and STAT3 activation and reduced the expression of STAT-dependent genes (chemokine/chemokine receptors, adhesion molecules, pro-inflammatory cytokines and scavenger receptors) in aortic tissue. Furthermore, atherosclerotic plaques exhibit a more stable phenotype characterized by lower lipids, T cells and M1 macrophages and higher M2 macrophages and collagen. Atheroprotection was accompanied by a systemic alteration of T helper- and T regulatory-related genes and a reduced activation state of circulating monocytes. In vascular smooth muscle cells and macrophages, SOCS gene delivery inhibited cytokine-induced STAT activation, pro-inflammatory gene expression, cell migration and proliferation. In conclusion, targeting SOCS proteins, predominantly SOCS1, to suppress pathological mechanisms involved in atheroma plaque progression and destabilization could be an interesting anti-atherosclerotic strategy.
ISSN: 0300-8428
DOI: 10.1007/s00395-014-0458-1
Source: Basic Research in Cardiology [ISSN 0300-8428], v. 110, 8
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