title: Oncostatin M receptor β deficiency attenuates atherogenesis by inhibiting JAK2/STAT3 signaling in macrophages.
abstract: Oncostatin M (OSM) is a secreted cytokine mainly involved in chronic inflammatory and cardiovascular diseases through binding to OSM receptor β (OSMR-β). Recent studies demonstrated that the presence of OSM contributed to the destabilization of atherosclerotic plaque. To investigate whether OSMR-β deficiency affects atherosclerosis, male OSMR-β-/-ApoE-/-mice were generated and utilized. Here we observed that OSMR-β expression was remarkably upregulated in both human and mouse atherosclerotic lesions, which were mainly located in macrophages. We found that OSMR-β deficiency significantly ameliorated atherosclerotic burden in aorta and aortic root relative to ApoE-deficient littermates and enhanced the stability of atherosclerotic plaques by increasing collagen and smooth muscle cell content, while decreasing macrophage infiltration and lipid accumulation. Moreover, bone marrow transplantation of OSMR-β-/-hematopoietic cells to atherosclerosis-prone mice displayed a consistent phenotype. Additionally, we observed a relatively reduced level of JAK2 and signal transducer and activator of transcription (STAT)3 in vivo and under Ox-LDL stimulation in vitro. Our findings suggest that OSMR-β deficiency in macrophages improved high-fat diet-induced atherogenesis and plaque vulnerability. Mech-anistically, the protective effect of OSMR-β deficiency on atherosclerosis may be partially attributed to the inhibition of the JAK2/STAT3 activation in macrophages, whereas OSM stimulation can activate the signaling pathway.
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.|Institute of Model Animals, Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.|Institute of Model Animals, Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Qin
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.|Institute of Model Animals, Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.|Institute of Model Animals, Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Xueyong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.
authors.forename: Fu-Han
authors.initials: FH
authors.lastname: Gong
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China.|Institute of Model Animals, Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: She
authors.affiliation: College of Life Science, Wuhan University, Wuhan, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China xiahao1966@163.com lihl@whu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, China xiahao1966@163.com lihl@whu.edu.cn.|Institute of Model Animals, Wuhan University, Wuhan, China.|Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000378:metabolism; D053681:Oncostatin M Receptor beta Subunit / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D053681:Oncostatin M Receptor beta Subunit; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2
keywords: Janus kinase 2/signal transducer and activator of transcription 3; atherosclerosis; inflammation