Nuclear factor-κB (NF-κB) is a key regulator of systematic inflammation in atherosclerosis (AS). The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, has emerged as an important regulator of chronic inflammation. However, the relationship between mTOR and NF-κB remains poorly defined. The aim of the present study was to investigate the role of mTOR in the pro-inflammatory pathway of human monocytes (HMCs) in patients with coronary artery disease (CAD) and to determine the interaction between mTOR and NF-κB signalling in the inflammatory state. HMCs were isolated from fasting blood samples of 68 patients with CAD and 59 subjects without CAD (non-CAD) to test the activity of NF-κB, p65 nuclear translocation and mTOR phosphorylation, which were all significantly elevated in the CAD group compared with those in the non-CAD group. The concentrations of serum interleukin (IL)-6 and tumour necrosis factor (TNF)-α were higher in the CAD group than in the non-CAD group. In an in vitro experiment, HMCs isolated from non-CAD subjects were used as culture model and were treated with sera extracted from CAD patients (CAD sera) or non-CAD subjects (con sera). CAD sera induced time-dependent phosphorylation of mTOR, aberrant NF-κB activation, as well as up-regulation of inflammatory factors. Moreover, inhibition of mTOR by pharmacological or genetic means abolished the CAD sera-triggered NF-κB activation and pro-inflammatory response. Furthermore, lipid-lowering drug statins partly blocked the CAD sera-activated mTOR and pro-inflammatory response. Our results show that CAD patients are in the pro-inflammatory state with increased NF-κB binding activity and enhanced mTOR phosphorylation. We also found that the activation of mTOR is required for the pro-inflammatory response via NF-κB-dependent pathway in HMCs, which unveils the underlying mechanism of AS and potential strategies to attenuate AS in clinical practice.
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Research Article|
January 23 2015
The activation of mTOR is required for monocyte pro-inflammatory response in patients with coronary artery disease
Shanshan Gao;
Shanshan Gao
1
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Weimin Liu;
Weimin Liu
1
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Xiaozhen Zhuo;
Xiaozhen Zhuo
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Lijun Wang;
Lijun Wang
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Gang Wang;
Gang Wang
†Department of Cardiology, Second Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710004, China
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Tao Sun;
Tao Sun
‡Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Shaanxi Xi’an 710038, China
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Zhao Zhao;
Zhao Zhao
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Junhui Liu;
Junhui Liu
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Yuling Tian;
Yuling Tian
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Juan Zhou;
Juan Zhou
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
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Zuyi Yuan;
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
Correspondence: Dr Yue Wu (email imyuewu@gmail.com) or Prof Zuyi Yuan (email zuyiyuan@mail.xjtu.edu.cn).
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Yue Wu
*Department of Cardiology, First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi Xi’an 710061, China
Correspondence: Dr Yue Wu (email imyuewu@gmail.com) or Prof Zuyi Yuan (email zuyiyuan@mail.xjtu.edu.cn).
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Publisher: Portland Press Ltd
Received:
July 11 2014
Revision Received:
October 23 2014
Accepted:
November 27 2014
Accepted Manuscript online:
November 27 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 128 (8): 517–526.
Article history
Received:
July 11 2014
Revision Received:
October 23 2014
Accepted:
November 27 2014
Accepted Manuscript online:
November 27 2014
Citation
Shanshan Gao, Weimin Liu, Xiaozhen Zhuo, Lijun Wang, Gang Wang, Tao Sun, Zhao Zhao, Junhui Liu, Yuling Tian, Juan Zhou, Zuyi Yuan, Yue Wu; The activation of mTOR is required for monocyte pro-inflammatory response in patients with coronary artery disease. Clin Sci (Lond) 1 April 2015; 128 (8): 517–526. doi: https://doi.org/10.1042/CS20140427
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