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Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice

Hyperglycemia in diabetes mellitus impairs endothelial function and disrupts microRNA (miRNA) profiles in vasculature, increasing the risk of diabetes-associated complications, including coronary artery disease, diabetic retinopathy, and diabetic nephropathy. miR-181b was previously reported to be a...

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Autores principales: Cheng, Chak-Kwong, Shang, Wenbin, Liu, Jian, Cheang, Wai-San, Wang, Yu, Xiang, Li, Lau, Chi-Wai, Luo, Jiang-Yun, Ng, Chi-Fai, Huang, Yu, Wang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220246/
https://www.ncbi.nlm.nih.gov/pubmed/35740034
http://dx.doi.org/10.3390/antiox11061137
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author Cheng, Chak-Kwong
Shang, Wenbin
Liu, Jian
Cheang, Wai-San
Wang, Yu
Xiang, Li
Lau, Chi-Wai
Luo, Jiang-Yun
Ng, Chi-Fai
Huang, Yu
Wang, Li
author_facet Cheng, Chak-Kwong
Shang, Wenbin
Liu, Jian
Cheang, Wai-San
Wang, Yu
Xiang, Li
Lau, Chi-Wai
Luo, Jiang-Yun
Ng, Chi-Fai
Huang, Yu
Wang, Li
author_sort Cheng, Chak-Kwong
collection PubMed
description Hyperglycemia in diabetes mellitus impairs endothelial function and disrupts microRNA (miRNA) profiles in vasculature, increasing the risk of diabetes-associated complications, including coronary artery disease, diabetic retinopathy, and diabetic nephropathy. miR-181b was previously reported to be an anti-inflammatory mediator in vasculature against atherosclerosis. The current study aimed to investigate whether miR-181b ameliorates diabetes-associated endothelial dysfunction, and to identify potential molecular mechanisms and upstream inducer of miR-181b. We found that miR-181b level was decreased in renal arteries of diabetic patients and in advanced glycation end products (AGEs)-treated renal arteries of non-diabetic patients. Transfection of miR-181b mimics improved endothelium-dependent vasodilation in aortas of high fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice, accompanied by suppression of superoxide overproduction and vascular inflammation markers. AMPK activator-induced AMPK activation upregulated miR-181b level in human umbilical vein endothelial cells (HUVECs). Chronic exercise, potentially through increased blood flow, activated AMPK/miR-181b axis in aortas of diabetic mice. Exposure to laminar shear stress upregulated miR-181b expression in HUVECs. Overall, our findings highlight a critical role of AMPK/miR-181b axis and extend the benefits of chronic exercise in counteracting diabetes-associated endothelial dysfunction.
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spelling pubmed-92202462022-06-24 Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice Cheng, Chak-Kwong Shang, Wenbin Liu, Jian Cheang, Wai-San Wang, Yu Xiang, Li Lau, Chi-Wai Luo, Jiang-Yun Ng, Chi-Fai Huang, Yu Wang, Li Antioxidants (Basel) Article Hyperglycemia in diabetes mellitus impairs endothelial function and disrupts microRNA (miRNA) profiles in vasculature, increasing the risk of diabetes-associated complications, including coronary artery disease, diabetic retinopathy, and diabetic nephropathy. miR-181b was previously reported to be an anti-inflammatory mediator in vasculature against atherosclerosis. The current study aimed to investigate whether miR-181b ameliorates diabetes-associated endothelial dysfunction, and to identify potential molecular mechanisms and upstream inducer of miR-181b. We found that miR-181b level was decreased in renal arteries of diabetic patients and in advanced glycation end products (AGEs)-treated renal arteries of non-diabetic patients. Transfection of miR-181b mimics improved endothelium-dependent vasodilation in aortas of high fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice, accompanied by suppression of superoxide overproduction and vascular inflammation markers. AMPK activator-induced AMPK activation upregulated miR-181b level in human umbilical vein endothelial cells (HUVECs). Chronic exercise, potentially through increased blood flow, activated AMPK/miR-181b axis in aortas of diabetic mice. Exposure to laminar shear stress upregulated miR-181b expression in HUVECs. Overall, our findings highlight a critical role of AMPK/miR-181b axis and extend the benefits of chronic exercise in counteracting diabetes-associated endothelial dysfunction. MDPI 2022-06-09 /pmc/articles/PMC9220246/ /pubmed/35740034 http://dx.doi.org/10.3390/antiox11061137 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Chak-Kwong
Shang, Wenbin
Liu, Jian
Cheang, Wai-San
Wang, Yu
Xiang, Li
Lau, Chi-Wai
Luo, Jiang-Yun
Ng, Chi-Fai
Huang, Yu
Wang, Li
Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice
title Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice
title_full Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice
title_fullStr Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice
title_full_unstemmed Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice
title_short Activation of AMPK/miR-181b Axis Alleviates Endothelial Dysfunction and Vascular Inflammation in Diabetic Mice
title_sort activation of ampk/mir-181b axis alleviates endothelial dysfunction and vascular inflammation in diabetic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220246/
https://www.ncbi.nlm.nih.gov/pubmed/35740034
http://dx.doi.org/10.3390/antiox11061137
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