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THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION

Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. In our previous study, a panel of miRNA including miR-134-5p was deregulated in young acute coronary syndrome (ACS) patients. However, the roles of these ACS-associated miRNAs in endothelial dysfunct...

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Main Authors: Tong, Kind-Leng, Zuhdi, Ahmad Syadi Mahmood, Wong, Pooi-Fong
Format: Article
Published: Leibniz Research Centre for Working Environment and Human Factors 2024
Subjects:
R Medicine (General)
Online Access:http://eprints.um.edu.my/47122/
https://doi.org/10.17179/excli2024-7342
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spelling my.um.eprints.471222024-11-28T04:13:11Z http://eprints.um.edu.my/47122/ THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION Tong, Kind-Leng Zuhdi, Ahmad Syadi Mahmood Wong, Pooi-Fong R Medicine (General) Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. In our previous study, a panel of miRNA including miR-134-5p was deregulated in young acute coronary syndrome (ACS) patients. However, the roles of these ACS-associated miRNAs in endothelial dysfunction, an early event preceding atherosclerosis, remain to be investigated. In the present study, human aortic endothelial cells (HAECs) were treated with 7-ketocholesterol (7-KC) to induce endothelial dysfunction. Following treatment with 20 mu g/ml 7KC, miR-134-5p was significantly up-regulated and endothelial nitric oxide synthase (eNOS) expression was suppressed. Endothelial barrier disruption was evidenced by the deregulation of adhesion molecules including the activation of focal adhesion kinase (FAK), down-regulation of VE-cadherin, up-regulation of adhesion molecules (E-selectin and ICAM-1), increased expression of inflammatory genes (IL1B, IL6 and COX2) and AKT activation. Knockdown of miR-134-5p in 7-KC-treated HAECs attenuated the suppression of eNOS, the activation of AKT, the down-regulation of VE-cadherin and the up-regulation of E-selectin. In addition, the interaction between miR134-5p and FOXM1 mRNA was confirmed by the enrichment of FOXM1 transcripts in the pull-down miRNAmRNA complex. Knockdown of miR-134-5p increased FOXM1 expression whereas transfection with mimic miR134-5p decreased FOXM1 protein expression. In summary, the involvement of an ACS-associated miRNA, miR134-5p in endothelial dysfunction was demonstrated. Findings from this study could pave future investigations into utilizing miRNAs as a supplementary tool in ACS diagnosis or as targets for the development of therapeutics. Leibniz Research Centre for Working Environment and Human Factors 2024 Article PeerReviewed Tong, Kind-Leng and Zuhdi, Ahmad Syadi Mahmood and Wong, Pooi-Fong (2024) THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION. EXCLI Journal, 23. pp. 1073-1090. ISSN 1611-2156, DOI https://doi.org/10.17179/excli2024-7342 <https://doi.org/10.17179/excli2024-7342>. https://doi.org/10.17179/excli2024-7342 10.17179/excli2024-7342
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine (General)
spellingShingle R Medicine (General)
Tong, Kind-Leng
Zuhdi, Ahmad Syadi Mahmood
Wong, Pooi-Fong
THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION
description Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. In our previous study, a panel of miRNA including miR-134-5p was deregulated in young acute coronary syndrome (ACS) patients. However, the roles of these ACS-associated miRNAs in endothelial dysfunction, an early event preceding atherosclerosis, remain to be investigated. In the present study, human aortic endothelial cells (HAECs) were treated with 7-ketocholesterol (7-KC) to induce endothelial dysfunction. Following treatment with 20 mu g/ml 7KC, miR-134-5p was significantly up-regulated and endothelial nitric oxide synthase (eNOS) expression was suppressed. Endothelial barrier disruption was evidenced by the deregulation of adhesion molecules including the activation of focal adhesion kinase (FAK), down-regulation of VE-cadherin, up-regulation of adhesion molecules (E-selectin and ICAM-1), increased expression of inflammatory genes (IL1B, IL6 and COX2) and AKT activation. Knockdown of miR-134-5p in 7-KC-treated HAECs attenuated the suppression of eNOS, the activation of AKT, the down-regulation of VE-cadherin and the up-regulation of E-selectin. In addition, the interaction between miR134-5p and FOXM1 mRNA was confirmed by the enrichment of FOXM1 transcripts in the pull-down miRNAmRNA complex. Knockdown of miR-134-5p increased FOXM1 expression whereas transfection with mimic miR134-5p decreased FOXM1 protein expression. In summary, the involvement of an ACS-associated miRNA, miR134-5p in endothelial dysfunction was demonstrated. Findings from this study could pave future investigations into utilizing miRNAs as a supplementary tool in ACS diagnosis or as targets for the development of therapeutics.
format Article
author Tong, Kind-Leng
Zuhdi, Ahmad Syadi Mahmood
Wong, Pooi-Fong
author_facet Tong, Kind-Leng
Zuhdi, Ahmad Syadi Mahmood
Wong, Pooi-Fong
author_sort Tong, Kind-Leng
title THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION
title_short THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION
title_full THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION
title_fullStr THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION
title_full_unstemmed THE ROLE OF MIR-134-5P IN 7-KETOCHOLESTEROL-INDUCED HUMAN AORTIC ENDOTHELIAL DYSFUNCTION
title_sort role of mir-134-5p in 7-ketocholesterol-induced human aortic endothelial dysfunction
publisher Leibniz Research Centre for Working Environment and Human Factors
publishDate 2024
url http://eprints.um.edu.my/47122/
https://doi.org/10.17179/excli2024-7342
_version_ 1817841983872303104
score 13.226497

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