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: Xin Zhang, Jing Li, Juan-Juan Qin, Wen-Lin Cheng, Xueyong Zhu, Fu-Han Gong, Zhigang She, Zan Huang, Hao Xia, Hongliang Li
• Journal: Journal of lipid research (J Lipid Res) Vol. 58 Issue 5 Pg. 895-906 (05 2017) ISSN: 1539-7262 [Electronic] United States
• PMID: 28258089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Oncostatin M Receptor beta Subunit
• STAT3 Transcription Factor
• Janus Kinase 2

Topics

• Animals
• Atherosclerosis (genetics, metabolism, pathology)
• Gene Expression Regulation
• Gene Knockout Techniques
• Humans
• Janus Kinase 2 (metabolism)
• Macrophages (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Necrosis (metabolism)
• Oncostatin M Receptor beta Subunit (deficiency, genetics, metabolism)
• Plaque, Atherosclerotic (metabolism, pathology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction