Multiple roles of SOCS proteins: differential expression of SOCS1 and SOCS3 in atherosclerosis

Pro-inflammatory cytokines play a key pathogenic role in atherosclerosis, which are induced by the Janus kinase/signal transducer and activator of transduction (JAK/STAT) pathway. Furthermore, the JAK/STAT pathway is negatively regulated by the suppressor of cytokine signaling (SOCS) proteins. However, the change in SOCS expression levels and the correlation between SOCS expression and cholesterol levels in atherosclerosis is not yet well understood. To this end, a mouse model of atherosclerosis was established using apolipoprotein-deficient (ApoE(-/-)) mice. The mice were fed either a chow or high-fat diet. The mRNA and protein expression of SOCS1 and SOCS3 in plaque and vessels were determined at different time points. Furthermore, SOCS1 and SOCS3 mRNA expression was detected in the peripheral blood mononuclear cells (PBMCs) obtained from 18 male subjects with no coronary heart disease (non-CHD) population. The expression of SOCS1 in the ApoE(-/-) mice first increased and then decreased and the high-fat diet accelerated the appearance of the peak; the expression of SOCS3 increased with the increased feeding duration, and this trend was more pronounced in the mice fed the high-fat diet. SOCS1/CD68 and SOCS3/CD68 showed opposite trends in expression with the increased duration of the high-fat diet. Interleukin-6 (IL-6) expression in the main aorta of the ApoE(-/-) mice fed the high-fat diet also increased with the increased feeding duration. In the non-CHD population, the total serum cholesterol levels positively correlated with SOCS3 mRNA expression in the PBMCs (r=0.433, P=0.012). These results demonstrate the differential expression of SOCS1 and SOCS3 in atherosclerosis and suggest that SOCS3, together with IL-6 may promote the formation and development of atherosclerosis.