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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Published in | EXCLI journal Vol. 23; pp. 1073 - 1090 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Germany
Leibniz Research Centre for Working Environment and Human Factors
01.01.2024
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Subjects | |
Online Access | Get full text |
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Summary: | 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 μg/ml 7-KC, 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 (
,
and
) 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 miR-134-5p and
mRNA was confirmed by the enrichment of
transcripts in the pull-down miRNA-mRNA complex. Knockdown of miR-134-5p increased
expression whereas transfection with mimic miR-134-5p decreased FOXM1 protein expression. In summary, the involvement of an ACS-associated miRNA, miR-134-5p 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1611-2156 1611-2156 |
DOI: | 10.17179/excli2024-7342 |