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Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors

AIMS: Proteasome-linked oxidative stress is believed to cause endothelial dysfunction, an early event in cardiovascular diseases (CVD). Statin, as HMG-CoA reductase inhibitor, prevents endothelial dysfunction in CVD. However, the molecular mechanism of statin-mediated normalization of endothelial fu...

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Autores principales: Wang, Fu, Ma, Hui, Liang, Wen-Jing, Yang, Jing-Jing, Wang, Xue-Qing, Shan, Mei-Rong, Chen, Yuan, Jia, Min, Yin, Ya-Ling, Sun, Xue-Ying, Zhang, Jia-Ning, Peng, Qi-Sheng, Chen, Yu-Guo, Liu, Li-Ying, Li, Peng, Guo, Tao, Wang, Shuang-Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354712/
https://www.ncbi.nlm.nih.gov/pubmed/28061433
http://dx.doi.org/10.18632/oncotarget.14462
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author Wang, Fu
Ma, Hui
Liang, Wen-Jing
Yang, Jing-Jing
Wang, Xue-Qing
Shan, Mei-Rong
Chen, Yuan
Jia, Min
Yin, Ya-Ling
Sun, Xue-Ying
Zhang, Jia-Ning
Peng, Qi-Sheng
Chen, Yu-Guo
Liu, Li-Ying
Li, Peng
Guo, Tao
Wang, Shuang-Xi
author_facet Wang, Fu
Ma, Hui
Liang, Wen-Jing
Yang, Jing-Jing
Wang, Xue-Qing
Shan, Mei-Rong
Chen, Yuan
Jia, Min
Yin, Ya-Ling
Sun, Xue-Ying
Zhang, Jia-Ning
Peng, Qi-Sheng
Chen, Yu-Guo
Liu, Li-Ying
Li, Peng
Guo, Tao
Wang, Shuang-Xi
author_sort Wang, Fu
collection PubMed
description AIMS: Proteasome-linked oxidative stress is believed to cause endothelial dysfunction, an early event in cardiovascular diseases (CVD). Statin, as HMG-CoA reductase inhibitor, prevents endothelial dysfunction in CVD. However, the molecular mechanism of statin-mediated normalization of endothelial function is not completely elucidated. METHODS AND RESULTS: Lovastatin time/dose-dependently increased miR-29b expression and decreased proteasome activity in cultured human umbilical vein endothelial cells (HUVECs). Anti-miR-29b or overexpression of PA200 abolished lovastatin-induced inhibition of proteasome activity in HUVECs. In contrast, pre-miR-29b or PA200 siRNA mimics these effects of lovastatin on proteasome activity. Lovastatin inhibited oxidative stress induced by multiple oxidants including ox-LDL, H(2)O(2), TNFa, homocysteine thiolactone (HTL), and high glucose (HG), which were reversed by inhibition of miR-29b in HUVECs. Ex vivo analysis indicated that lovastatin normalized the acetylcholine-induced endothelium-dependent relaxation and the redox status in isolated rat aortic arteries exposure to multiple cardiovascular risk factors. In vivo analysis revealed that administration of lovastatin remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats with hyperglycemia, dyslipidemia, and hyperhomocysteinemia, as well as increased miR-29b expressions, reduced PA200 protein levels, and suppression of proteasome activity in aortic tissues. CONCLUSION: Upregulation of miR-29b expression is a common mechanism contributing to endothelial dysfunction induced by multiple cardiovascular risk factors through PA200-dependent proteasome-mediated oxidative stress, which is prevented by lovastatin.
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spelling pubmed-53547122017-04-14 Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors Wang, Fu Ma, Hui Liang, Wen-Jing Yang, Jing-Jing Wang, Xue-Qing Shan, Mei-Rong Chen, Yuan Jia, Min Yin, Ya-Ling Sun, Xue-Ying Zhang, Jia-Ning Peng, Qi-Sheng Chen, Yu-Guo Liu, Li-Ying Li, Peng Guo, Tao Wang, Shuang-Xi Oncotarget Research Paper: Pathology AIMS: Proteasome-linked oxidative stress is believed to cause endothelial dysfunction, an early event in cardiovascular diseases (CVD). Statin, as HMG-CoA reductase inhibitor, prevents endothelial dysfunction in CVD. However, the molecular mechanism of statin-mediated normalization of endothelial function is not completely elucidated. METHODS AND RESULTS: Lovastatin time/dose-dependently increased miR-29b expression and decreased proteasome activity in cultured human umbilical vein endothelial cells (HUVECs). Anti-miR-29b or overexpression of PA200 abolished lovastatin-induced inhibition of proteasome activity in HUVECs. In contrast, pre-miR-29b or PA200 siRNA mimics these effects of lovastatin on proteasome activity. Lovastatin inhibited oxidative stress induced by multiple oxidants including ox-LDL, H(2)O(2), TNFa, homocysteine thiolactone (HTL), and high glucose (HG), which were reversed by inhibition of miR-29b in HUVECs. Ex vivo analysis indicated that lovastatin normalized the acetylcholine-induced endothelium-dependent relaxation and the redox status in isolated rat aortic arteries exposure to multiple cardiovascular risk factors. In vivo analysis revealed that administration of lovastatin remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats with hyperglycemia, dyslipidemia, and hyperhomocysteinemia, as well as increased miR-29b expressions, reduced PA200 protein levels, and suppression of proteasome activity in aortic tissues. CONCLUSION: Upregulation of miR-29b expression is a common mechanism contributing to endothelial dysfunction induced by multiple cardiovascular risk factors through PA200-dependent proteasome-mediated oxidative stress, which is prevented by lovastatin. Impact Journals LLC 2017-01-03 /pmc/articles/PMC5354712/ /pubmed/28061433 http://dx.doi.org/10.18632/oncotarget.14462 Text en Copyright: © 2017 Wang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Pathology
Wang, Fu
Ma, Hui
Liang, Wen-Jing
Yang, Jing-Jing
Wang, Xue-Qing
Shan, Mei-Rong
Chen, Yuan
Jia, Min
Yin, Ya-Ling
Sun, Xue-Ying
Zhang, Jia-Ning
Peng, Qi-Sheng
Chen, Yu-Guo
Liu, Li-Ying
Li, Peng
Guo, Tao
Wang, Shuang-Xi
Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors
title Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors
title_full Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors
title_fullStr Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors
title_full_unstemmed Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors
title_short Lovastatin upregulates microRNA-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors
title_sort lovastatin upregulates microrna-29b to reduce oxidative stress in rats with multiple cardiovascular risk factors
topic Research Paper: Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354712/
https://www.ncbi.nlm.nih.gov/pubmed/28061433
http://dx.doi.org/10.18632/oncotarget.14462
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