Department of Surgery, Division of Vascular Surgery, VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle, WA, USA.
Atherosclerosis. 2011 Jun;216(2):292-8. doi: 10.1016/j.atherosclerosis.2011.02.003. Epub 2011 Mar 3.
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 Oncostatin M (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.
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.
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.
慢性炎症在动脉粥样硬化的发生和发展中起着关键作用。炎症反应是由细胞因子介导的。本研究旨在确定单核细胞和 T 淋巴细胞特异性细胞因子——肿瘤坏死因子相关诱导因子（Oncostatin M，OSM）是否存在于动脉粥样硬化病变中。我们还研究了信号转导子和转录激活子（signal transducer and activator of transcription，STAT）-1 和 STAT-3 在调节 OSM 诱导的平滑肌细胞（smooth muscle cell，SMC）增殖、迁移和细胞纤维连接蛋白（cellular fibronectin，cFN）合成中的作用。
对人颈动脉斑块动脉粥样硬化病变的免疫染色显示，OSM 抗原在巨噬细胞和 SMC 中均有表达。通过 RT-PCR 和 Western blot 检测，从人颈动脉斑块中分离出的培养 SMC 表达 OSM mRNA 和蛋白。利用动脉粥样硬化的 ApoE(-/-) 小鼠模型，我们观察到 OSM 最初在 20 周龄的内膜中表达。到 30 周时，OSM 在内膜和中膜中均有表达。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 抑制可防止 OSM 诱导的 SMC 增殖、迁移和细胞纤维连接蛋白合成。
这些发现表明，OSM 在动脉粥样硬化病变中表达，并通过 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。
