Oncostatin M is expressed in atherosclerotic lesions: A role for Oncostatin M in the pathogenesis of atherosclerosis
Oncostatin M is expressed in atherosclerotic lesions: A role for Oncostatin M in the pathogenesis of atherosclerosis
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DOI：
10.1016/j.atherosclerosis.2011.02.003
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发表时间：
2011-06-01
期刊：
影响因子：
5.3
通讯作者：
Wijelath, Errol S.
中科院分区：
文献类型：
--
作者：
Albasanz-Puig, Adaia;Murray, Jacqueline;Wijelath, Errol S.
目的：慢性炎症在动脉粥样硬化的发生和进展中起着关键作用。炎症反应由细胞因子介导。本研究的目的是确定动脉粥样硬化病变中是否存在制瘤素 M (OSM)（一种单核细胞和 T 淋巴细胞特异性细胞因子）。我们还研究了信号转导子和转录激活子（STAT）-1和STAT-3在调节OSM诱导的平滑肌细胞（SMC）增殖、迁移和细胞纤连蛋白（cFN）合成中的作用。方法和结果：对人颈动脉斑块的动脉粥样硬化病变进行免疫染色，证明巨噬细胞和SMC中都有OSM抗原的表达。通过 RT-PCR 和蛋白质印迹法测定，从人颈动脉斑块中移植的 SMC 表达 OSM mRNA 和蛋白质。使用食物喂养的 ApoE-/- 小鼠动脉粥样硬化模型，我们观察到 OSM 最初在 20 周龄时在内膜中表达。到 30 周时，OSM 在内膜和中膜中均表达。体外研究表明，OSM 促进 SMC 增殖、迁移和 cFN 合成。慢病毒介导的STAT-1和STAT-3抑制可阻止OSM诱导的SMC增殖、迁移和细胞纤连蛋白合成。结论：这些研究结果表明OSM在动脉粥样硬化病变中表达，可能通过STAT途径促进SMC增殖、迁移和细胞外基质蛋白合成，从而促进动脉粥样硬化的进展。由爱思唯尔爱尔兰有限公司出版
Objective: Chronic inflammation plays a pivotal role in the development and progression of atherosclerosis. The inflammatory response is mediated by cytokines. The aim of this study was to determine if OncostatinM(OSM), a monocyte and T-lymphocyte specific cytokine is present in atherosclerotic lesions. We also investigated the roles of signal transducer and activator of transcription (STAT)-1 and STAT-3 in regulating OSM-induced smooth muscle cell (SMC) proliferation, migration and cellular fibronectin (cFN) synthesis.Methods and results: Immunostaining of atherosclerotic lesions from human carotid plaques demonstrated the expression of OSM antigen in both macrophages and SMCs. Explanted SMCs from human carotid plaques expressed OSM mRNA and protein as determined by RT-PCR and Western blotting. Using the chow-fed ApoE-/- mouse model of atherosclerosis, we observed that OSM was initially expressed in the intima at 20 weeks of age. By 30 weeks, OSM was expressed in both the intima and media. In vitro studies show that OSM promotes SMC proliferation, migration and cFN synthesis. Lentivirus mediated-inhibition of STAT-1 and STAT-3 prevented OSM-induced SMC proliferation, migration and cellular fibronectin synthesis.Conclusions: These findings demonstrate that OSM is expressed in atherosclerotic lesions and may contribute to the progression of atherosclerosis by promoting SMC proliferation, migration and extracellular matrix protein synthesis through the STAT pathway. Published by Elsevier Ireland Ltd.