title: Multiple roles of SOCS proteins: differential expression of SOCS1 and SOCS3 in atherosclerosis.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Tian
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Zu-Yi
authors.initials: ZY
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D013194:Staining and Labeling; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D002784:Cholesterol