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Irisin Alleviates Advanced Glycation End Products-Induced Inflammation and Endothelial Dysfunction via Inhibiting ROS-NLRP3 Inflammasome Signaling

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Abstract

The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome have been implicated in the initiation or progression of atherosclerosis. Recent research showed that irisin, a newly discovered adipomiokine, alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses, suggesting that irisin may be a promising candidate for the treatment of vascular complications of diabetes. However, the association between irisin and NLRP3 inflammasome in the pathogenesis of atherosclerosis remains unclear. In the present study, we cultured human umbilical vein endothelial cells (HUVECs) in advanced glycation end products (AGEs) medium; exogenous irisin (0.01, 0.1, 1 μg/ml) were used as an intervention reagent. siRNA and adenoviral vector were constructed to realize silencing and over-expression of NLRP3 gene. Our data showed that irisin significantly reversed AGEs-induced oxidative stress and NLRP3 inflammasome signaling activation (p < 0.05), and increased the endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production in a dose-dependent manner (p < 0.05). siRNA-mediated knockdown NLRP3 facilitated the irisin-mediated anti-inflammatory and antiatherogenic effects (p < 0.05). However, these irisin-mediated effects were reversed by over-expression NLRP3 (p < 0.05). Taken together, our results reveal that irisin alleviates AGEs-induced inflammation and endothelial dysfunction via inhibiting ROS-NLRP3 inflammasome signaling, suggest a likely mechanism for irisin-induced therapeutic effect in vascular complications of diabetes.

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Acknowledgements

We would like to thank the Center of Peripheral Vascular Surgery (Affiliated Hospital of Southwest Medical University).

Funding

This work was supported by the Office of Science Technology and Intellectual Property of Luzhou (No. 14141) and the Program of the Affiliated Hospital of Southwest Medical University (No. 14070).

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Authors and Affiliations

  1. Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, People’s Republic of China

    Xian Deng, Wei Huang, Ting-Ting Zhu, Xiao-Lei Sun, Jian-Feng Xiong, Hu-Qiang He & You-Hua Xu

  2. State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Avenida Wai Long, Taipa, Macau, People’s Republic of China

    Xian Deng, Wei Huang, Ting-Ting Zhu, Xiao-Lei Sun, Jian-Feng Xiong, Hu-Qiang He & You-Hua Xu

  3. Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China

    Xian Deng, Xiao-Lei Sun, Xiang-Yu Zhou, Hui Yang, Hu-Qiang He & Yan-Zheng He

  4. Department of Endocrinology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China

    Wei Huang

  5. Department of Rehabilitation, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China

    Juan Peng

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  1. Xian Deng
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  3. Juan Peng
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Correspondence to You-Hua Xu or Yan-Zheng He.

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Wei Huang is co-first author.

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Deng, X., Huang, W., Peng, J. et al. Irisin Alleviates Advanced Glycation End Products-Induced Inflammation and Endothelial Dysfunction via Inhibiting ROS-NLRP3 Inflammasome Signaling. Inflammation 41, 260–275 (2018). https://doi.org/10.1007/s10753-017-0685-3

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  • DOI: https://doi.org/10.1007/s10753-017-0685-3

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