Gene delivery of suppressors of cytokine signaling (SOCS) inhibits inflammation and atherosclerosis development in mice.

摘要: Chronic activation of Janus kinase/signal transducers and activators transcription (JAK/STAT) pathway contributes to vascular inflammation atherosclerosis by inducing expression genes involved in cell proliferation, differentiation migration. We aimed investigate whether enforced negative regulators, the suppressors cytokine signaling (SOCS1 SOCS3), inhibits harmful JAK/STAT-mediated responses affects apolipoprotein E knockout mice. Adenovirus-mediated SOCS1 transgene impaired onset progression without impact on lipid profile, whereas SOCS3 was only effective early atherosclerosis. Mechanistically, SOCS gene delivery, primarily SOCS1, attenuated STAT1 STAT3 reduced STAT-dependent (chemokine/chemokine receptors, adhesion molecules, pro-inflammatory cytokines scavenger receptors) aortic tissue. Furthermore, atherosclerotic plaques exhibit a more stable phenotype characterized lower lipids, T cells M1 macrophages higher M2 collagen. Atheroprotection accompanied systemic alteration helper- regulatory-related state circulating monocytes. In smooth muscle macrophages, delivery inhibited cytokine-induced STAT activation, expression, migration proliferation. conclusion, targeting proteins, predominantly suppress pathological mechanisms atheroma plaque destabilization could be an interesting anti-atherosclerotic strategy.