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Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm
Aim: Smoking is a major risk factor for abdominal aortic aneurysm (AAA). Among the components of smoke, nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms throu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379742/ https://www.ncbi.nlm.nih.gov/pubmed/32765304 http://dx.doi.org/10.3389/fphys.2020.00866 |
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author | Duan, Liren Li, Shenli Wang, Lei Jing, Yuchen Li, Guangxin Sun, Yaodong Sun, Weifeng Li, Yalun Zhao, Lin Xin, Shijie |
author_facet | Duan, Liren Li, Shenli Wang, Lei Jing, Yuchen Li, Guangxin Sun, Yaodong Sun, Weifeng Li, Yalun Zhao, Lin Xin, Shijie |
author_sort | Duan, Liren |
collection | PubMed |
description | Aim: Smoking is a major risk factor for abdominal aortic aneurysm (AAA). Among the components of smoke, nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms through which nicotine induces vascular wall dysfunction and to examine whether melatonin protects against nicotine-related AAA. Methods: In this study, an enzyme-linked immunosorbent assay (ELISA) was used to measure melatonin and TNF-α levels, as well as total antioxidant status (TAS), in patients with AAA. We established a nicotine-related AAA model and explored the mechanisms underlying the therapeutic effects of melatonin. Tissue histopathology was used to assess vascular function, while western blotting (WB) and immunofluorescence staining were performed to detect protein expression. Results: We observed melatonin insufficiency in the serum from patients with AAA, particularly smokers. Moreover, melatonin level was positively correlated with antioxidant capacity. In the in vivo model, nicotine accelerated AAA expansion and destroyed vascular structure. Furthermore, OPN, LC3II, p62, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), NF-κB p65, TNF-α, phosphorylated AKT, and phosphorylated mTOR levels were increased, in vivo, following nicotine treatment, while SM22α and α-SMA levels were reduced. Additionally, melatonin attenuated the effects of nicotine on AAA and reversed changes in protein expression. Moreover, melatonin lost its protective effects following bafilomycin A1-mediated inhibition of autophagy. Conclusion: Based on our data, melatonin exerts a beneficial effect on rats with nicotine-related AAA by downregulating the AKT-mTOR signaling pathway, improving autophagy dysfunction, and restoring the VSMC phenotype. |
format | Online Article Text |
id | pubmed-7379742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73797422020-08-05 Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm Duan, Liren Li, Shenli Wang, Lei Jing, Yuchen Li, Guangxin Sun, Yaodong Sun, Weifeng Li, Yalun Zhao, Lin Xin, Shijie Front Physiol Physiology Aim: Smoking is a major risk factor for abdominal aortic aneurysm (AAA). Among the components of smoke, nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms through which nicotine induces vascular wall dysfunction and to examine whether melatonin protects against nicotine-related AAA. Methods: In this study, an enzyme-linked immunosorbent assay (ELISA) was used to measure melatonin and TNF-α levels, as well as total antioxidant status (TAS), in patients with AAA. We established a nicotine-related AAA model and explored the mechanisms underlying the therapeutic effects of melatonin. Tissue histopathology was used to assess vascular function, while western blotting (WB) and immunofluorescence staining were performed to detect protein expression. Results: We observed melatonin insufficiency in the serum from patients with AAA, particularly smokers. Moreover, melatonin level was positively correlated with antioxidant capacity. In the in vivo model, nicotine accelerated AAA expansion and destroyed vascular structure. Furthermore, OPN, LC3II, p62, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), NF-κB p65, TNF-α, phosphorylated AKT, and phosphorylated mTOR levels were increased, in vivo, following nicotine treatment, while SM22α and α-SMA levels were reduced. Additionally, melatonin attenuated the effects of nicotine on AAA and reversed changes in protein expression. Moreover, melatonin lost its protective effects following bafilomycin A1-mediated inhibition of autophagy. Conclusion: Based on our data, melatonin exerts a beneficial effect on rats with nicotine-related AAA by downregulating the AKT-mTOR signaling pathway, improving autophagy dysfunction, and restoring the VSMC phenotype. Frontiers Media S.A. 2020-07-17 /pmc/articles/PMC7379742/ /pubmed/32765304 http://dx.doi.org/10.3389/fphys.2020.00866 Text en Copyright © 2020 Duan, Li, Wang, Jing, Li, Sun, Sun, Li, Zhao and Xin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Duan, Liren Li, Shenli Wang, Lei Jing, Yuchen Li, Guangxin Sun, Yaodong Sun, Weifeng Li, Yalun Zhao, Lin Xin, Shijie Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm |
title | Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm |
title_full | Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm |
title_fullStr | Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm |
title_full_unstemmed | Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm |
title_short | Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm |
title_sort | melatonin plays a critical protective role in nicotine-related abdominal aortic aneurysm |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379742/ https://www.ncbi.nlm.nih.gov/pubmed/32765304 http://dx.doi.org/10.3389/fphys.2020.00866 |
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