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: | , , |
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| Format: | Article |
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Leibniz Research Centre for Working Environment and Human Factors
2024
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| Online Access: | http://eprints.um.edu.my/47122/ https://doi.org/10.17179/excli2024-7342 |
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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 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. |
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