Activation of CD137 signaling accelerates vascular calcification in vivo and vitro
Activation of CD137 signaling accelerates vascular calcification in vivo and vitro
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CD137信号传导的激活加速体内和体外血管钙化
DOI：
10.1016/j.ijcard.2016.12.174
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发表时间：
2017-03-01
影响因子：
3.5
通讯作者：
Yan, Jinchuan
中科院分区：
文献类型：
--
作者：
Chen, Yao;Bangash, Abdul Basit;Yan, Jinchuan
目的：血管钙化是动脉粥样硬化的特征，被认为是心血管风险的独立预测因子。CD137信号已被证明与动脉粥样硬化有关。然而，CD137信号在调节血管钙化中的可能作用尚未见报道。在本研究中，我们研究了CD137信号在载脂蛋白E(-/-)小鼠血管钙化和小鼠血管平滑肌细胞(VSMCs)中的作用。方法：用von-Kossa和Masson‘s三色染色分别鉴定体内和体外的钙沉积和肌纤维。碱性磷酸酶(ALP)检测试剂盒检测ALP活性。用实时定量聚合酶链式反应、免疫印迹和免疫荧光检测BMP2和Runx2在体外和体内的表达。结果：CD137激动剂抗体激活CD137信号后，血管钙化面积增加。CD137信号通路的激活也增加了BMP2和Runx2在动脉粥样硬化斑块中的表达。在体外，激活CD137信号也可加重VSMC钙化，而阻断CD137信号可减轻激动剂CD137诱导的VSMC钙化。此外，钙化指标钙、BMP2和Runx2的水平在激动剂CD137组均显著升高。结论：CD137信号在体内和体外血管钙化中的作用未知，为今后防治动脉粥样硬化提供了新的靶点。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
Objectives: Vascular calcification is a characteristic feature of atherosclerosis and is considered as an independent predictor of cardiovascular risk. CD137 signaling has previously shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulation of vascular calcification has not been reported. In the present study, we investigated the effect of CD137 signaling on vascular calcification in ApoE(-/-)mice and in vascular smooth muscle cells (VSMCs) of mice.Methods: Calcium deposition and muscle fibers in vivo or vitro were identified by von-Kossa and Masson's trichrome staining respectively. Alkaline phosphatase (ALP) activity was measured by the ALP assay Kit. The presence of bone morphogenic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) was detected by real-time PCR, Western blot and immunofluorescence in vitro or vivo.Results: Our data shows that activation of CD137 signaling by intraperitoneal injection of agonist-CD137 antibody increased the areas of vascular calcification. Activation of CD137 signaling also increased the expression of BMP2 and Runx2 in the atherosclerotic plaques. In vitro, activation of CD137 signaling also aggravated VSMC calcification, while blocking CD137 signaling could alleviate agonist-CD137 induced VSMC calcification. In addition, the levels of calcium, BMP2 and Runx2, indicators of calcification, were all significantly elevated in agonist-CD137 group in VSMCs.Conclusion: Our data revealed a previously unrecognized role of CD137 signaling in vascular calcification in vivo and vitro and provides a novel target for prevention and treatment of atherosclerosis in the future. (C) 2016 Elsevier Ireland Ltd. All rights reserved.