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NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway

Hypertension is characterized by endothelial dysfunction, vascular remodeling, and rearrangement of the extracellular matrix. Besides, the pathogenesis of hypertension is closely related to excess generation of reactive oxygen species (ROS). Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-l...

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Autores principales: Zhou, Lei, Zhang, Sheng, Bolor-Erdene, Enkhbat, Wang, Lingwei, Tian, Ding, Mei, Yunqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791967/
https://www.ncbi.nlm.nih.gov/pubmed/33488923
http://dx.doi.org/10.1155/2020/1974265
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author Zhou, Lei
Zhang, Sheng
Bolor-Erdene, Enkhbat
Wang, Lingwei
Tian, Ding
Mei, Yunqing
author_facet Zhou, Lei
Zhang, Sheng
Bolor-Erdene, Enkhbat
Wang, Lingwei
Tian, Ding
Mei, Yunqing
author_sort Zhou, Lei
collection PubMed
description Hypertension is characterized by endothelial dysfunction, vascular remodeling, and rearrangement of the extracellular matrix. Besides, the pathogenesis of hypertension is closely related to excess generation of reactive oxygen species (ROS). Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis that influences the activity of NAD-dependent enzymes, such as sirtuins, which possess NAD-dependent protein deacetylase activity and cleave NAD during the deacetylation cycle. Recently, NAMPT has been shown to play a crucial role in various diseases associated with oxidative stress. However, the function and regulation of NAMPT in hypertension have not been extensively explored. In the present study, we identified NAMPT as a crucial regulator of hypertension, because NAMPT expression was significantly downregulated in both patients with hypertension and experimental animals. NAMPT knockout (NAMPT+/-) mice exhibited a significantly higher blood pressure and ROS levels after stimulation with angiotensin II (Ang II) than wild-type mice, and the administration of recombinant human NAMPT (rhNAMPT) reversed this effect. In vivo, overexpression of NAMPT protected against angiotensin II- (Ang II-) induced hypertension by inhibiting ROS production via sirtuin 1 in mouse aortic endothelial cells (MAECs) and mouse aortic vascular smooth muscle cells (MOVAs). In turn, NAMPT alleviated the ROS-induced mitogen-activated protein kinase (MAPK) pathway. In conclusion, NAMPT might be a novel biomarker and a therapeutic target in hypertension.
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spelling pubmed-77919672021-01-21 NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway Zhou, Lei Zhang, Sheng Bolor-Erdene, Enkhbat Wang, Lingwei Tian, Ding Mei, Yunqing Oxid Med Cell Longev Research Article Hypertension is characterized by endothelial dysfunction, vascular remodeling, and rearrangement of the extracellular matrix. Besides, the pathogenesis of hypertension is closely related to excess generation of reactive oxygen species (ROS). Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis that influences the activity of NAD-dependent enzymes, such as sirtuins, which possess NAD-dependent protein deacetylase activity and cleave NAD during the deacetylation cycle. Recently, NAMPT has been shown to play a crucial role in various diseases associated with oxidative stress. However, the function and regulation of NAMPT in hypertension have not been extensively explored. In the present study, we identified NAMPT as a crucial regulator of hypertension, because NAMPT expression was significantly downregulated in both patients with hypertension and experimental animals. NAMPT knockout (NAMPT+/-) mice exhibited a significantly higher blood pressure and ROS levels after stimulation with angiotensin II (Ang II) than wild-type mice, and the administration of recombinant human NAMPT (rhNAMPT) reversed this effect. In vivo, overexpression of NAMPT protected against angiotensin II- (Ang II-) induced hypertension by inhibiting ROS production via sirtuin 1 in mouse aortic endothelial cells (MAECs) and mouse aortic vascular smooth muscle cells (MOVAs). In turn, NAMPT alleviated the ROS-induced mitogen-activated protein kinase (MAPK) pathway. In conclusion, NAMPT might be a novel biomarker and a therapeutic target in hypertension. Hindawi 2020-12-30 /pmc/articles/PMC7791967/ /pubmed/33488923 http://dx.doi.org/10.1155/2020/1974265 Text en Copyright © 2020 Lei Zhou et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhou, Lei
Zhang, Sheng
Bolor-Erdene, Enkhbat
Wang, Lingwei
Tian, Ding
Mei, Yunqing
NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway
title NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway
title_full NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway
title_fullStr NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway
title_full_unstemmed NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway
title_short NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway
title_sort nampt/sirt1 attenuate ang ii-induced vascular remodeling and vulnerability to hypertension by inhibiting the ros/mapk pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791967/
https://www.ncbi.nlm.nih.gov/pubmed/33488923
http://dx.doi.org/10.1155/2020/1974265
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