title: Protein Inhibitor of Activated STAT3 Suppresses Oxidized LDL-induced Cell Responses during Atherosclerosis in Apolipoprotein E-deficient Mice.
abstract: Atherosclerosis is a serious public health concern. Excessive inflammatory responses of vascular cells are considered a pivotal pathogenesis mechanism underlying atherosclerosis development. It is known that Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signalling plays an important role in atherosclerosis progression. Protein inhibitor of activated STAT3 (PIAS3) is the key negative regulator of JAK/STAT3 signalling. However, its effect on atherogenesis is unknown. Here, we observed that PIAS3 levels are reduced in atherosclerotic lesions and that PIAS3 expression decreases in conjunction with increases in interleukin-6 expression and atherosclerosis severity. Oxidized low-density lipoprotein (ox-LDL), an atherogenic stimulus, reduced PIAS3 expression, an effect that may be attributed to nitric oxide synthesis upregulation. In turn, PIAS3 overexpression effectively suppressed ox-LDL-induced inflammation, lipid accumulation and vascular smooth muscle cell proliferation. These results indicate that PIAS3 is a critical repressor of atherosclerosis progression. The findings of this study have contributed to our understanding on the pathogenesis of atherosclerosis and have provided us with a potential target through which we can inhibit atherosclerosis-related cellular responses.
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA.
authors.forename: Yanjin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Liran
authors.initials: L
authors.lastname: Xu
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Bai
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Cardiology, Yanbian University Hospital, Yanji, Jilin 133000, China.
authors.forename: Xianwu
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D008077:Lipoproteins, LDL; C109279:Pias3 protein, mouse; D050828:Protein Inhibitors of Activated STAT; C577686:interleukin-6, mouse; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide