FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway
Vascular oxidative stress and inflammation play a major role in vascular diseases. This study was aimed at determining the protective roles of fibronectin type III domain-containing 5 (FNDC5) in angiotensin II- (Ang II-) induced vascular oxidative stress and inflammation and underlying mechanisms. W...
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2020-01-01
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Series: | Oxidative Medicine and Cellular Longevity |
Online Access: | http://dx.doi.org/10.1155/2020/6384803 |
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doaj-c0ec9fd7ba014cbb985763f98aa352b02020-11-25T03:14:07ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942020-01-01202010.1155/2020/63848036384803FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal PathwayBing Zhou0Yun Qiu1Nan Wu2Ai-Dong Chen3Hong Zhou4Qi Chen5Yu-Ming Kang6Yue-Hua Li7Guo-Qing Zhu8Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaDepartment of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaDepartment of Physiology and Pathophysiology, Cardiovascular Research Center, Xi’an Jiaotong University School of Medicine, Xi’an 710061, ChinaDepartment of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, and Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, ChinaVascular oxidative stress and inflammation play a major role in vascular diseases. This study was aimed at determining the protective roles of fibronectin type III domain-containing 5 (FNDC5) in angiotensin II- (Ang II-) induced vascular oxidative stress and inflammation and underlying mechanisms. Wild-type (WT) and FNDC5-/- mice, primary mouse vascular smooth muscle cells (VSMCs), and the rat aortic smooth muscle cell line (A7R5) were used in the present study. Subcutaneous infusion of Ang II caused more serious hypertension, vascular remodeling, oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in the aorta of FNDC5-/- mice than those of WT mice. Exogenous FNDC5 attenuated Ang II-induced superoxide generation, NADPH oxidase 2 (NOX2) and NLRP3 upregulation, mature caspase-1, and interleukin-1β (IL-1β) production in A7R5 cells. The protective roles of FNDC5 were prevented by SIRT-1 inhibitor EX527, AMPK inhibitor compound C, or integrin receptor inhibitor GLPG0187. FNDC5 attenuated the Ang II-induced inhibition in SIRT1 activity, SIRT1 protein expression, and AMPKα phosphorylation in A7R5 cells, which were prevented by compound C, EX527, and GLPG0187. FNDC5 deficiency deteriorated Ang II-induced oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in primary aortic VSMCs of mice, which were prevented by exogenous FNDC5. These results indicate that FNDC5 deficiency aggravates while exogenous FNDC5 alleviates the Ang II-induced vascular oxidative stress and NLRP3 inflammasome activation via the AMPK-SIRT1 signal pathway in VSMCs.http://dx.doi.org/10.1155/2020/6384803 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bing Zhou Yun Qiu Nan Wu Ai-Dong Chen Hong Zhou Qi Chen Yu-Ming Kang Yue-Hua Li Guo-Qing Zhu |
spellingShingle |
Bing Zhou Yun Qiu Nan Wu Ai-Dong Chen Hong Zhou Qi Chen Yu-Ming Kang Yue-Hua Li Guo-Qing Zhu FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway Oxidative Medicine and Cellular Longevity |
author_facet |
Bing Zhou Yun Qiu Nan Wu Ai-Dong Chen Hong Zhou Qi Chen Yu-Ming Kang Yue-Hua Li Guo-Qing Zhu |
author_sort |
Bing Zhou |
title |
FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway |
title_short |
FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway |
title_full |
FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway |
title_fullStr |
FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway |
title_full_unstemmed |
FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway |
title_sort |
fndc5 attenuates oxidative stress and nlrp3 inflammasome activation in vascular smooth muscle cells via activating the ampk-sirt1 signal pathway |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2020-01-01 |
description |
Vascular oxidative stress and inflammation play a major role in vascular diseases. This study was aimed at determining the protective roles of fibronectin type III domain-containing 5 (FNDC5) in angiotensin II- (Ang II-) induced vascular oxidative stress and inflammation and underlying mechanisms. Wild-type (WT) and FNDC5-/- mice, primary mouse vascular smooth muscle cells (VSMCs), and the rat aortic smooth muscle cell line (A7R5) were used in the present study. Subcutaneous infusion of Ang II caused more serious hypertension, vascular remodeling, oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in the aorta of FNDC5-/- mice than those of WT mice. Exogenous FNDC5 attenuated Ang II-induced superoxide generation, NADPH oxidase 2 (NOX2) and NLRP3 upregulation, mature caspase-1, and interleukin-1β (IL-1β) production in A7R5 cells. The protective roles of FNDC5 were prevented by SIRT-1 inhibitor EX527, AMPK inhibitor compound C, or integrin receptor inhibitor GLPG0187. FNDC5 attenuated the Ang II-induced inhibition in SIRT1 activity, SIRT1 protein expression, and AMPKα phosphorylation in A7R5 cells, which were prevented by compound C, EX527, and GLPG0187. FNDC5 deficiency deteriorated Ang II-induced oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in primary aortic VSMCs of mice, which were prevented by exogenous FNDC5. These results indicate that FNDC5 deficiency aggravates while exogenous FNDC5 alleviates the Ang II-induced vascular oxidative stress and NLRP3 inflammasome activation via the AMPK-SIRT1 signal pathway in VSMCs. |
url |
http://dx.doi.org/10.1155/2020/6384803 |
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