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MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis

BACKGROUND: Epicardial adipose tissue (EAT) shares the same microcirculation with coronary arteries through coronary arteries branches, and contributes to the development of atherosclerosis. MicroRNAs (miRNAs) are involved in the formation of atherosclerosis. However, the alteration of miRNA profile...

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Autores principales: Zhang, Fan, Cheng, Naixuan, Du, Jie, Zhang, Haibo, Zhang, Congcong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042726/
https://www.ncbi.nlm.nih.gov/pubmed/33845782
http://dx.doi.org/10.1186/s12872-021-01980-0
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author Zhang, Fan
Cheng, Naixuan
Du, Jie
Zhang, Haibo
Zhang, Congcong
author_facet Zhang, Fan
Cheng, Naixuan
Du, Jie
Zhang, Haibo
Zhang, Congcong
author_sort Zhang, Fan
collection PubMed
description BACKGROUND: Epicardial adipose tissue (EAT) shares the same microcirculation with coronary arteries through coronary arteries branches, and contributes to the development of atherosclerosis. MicroRNAs (miRNAs) are involved in the formation of atherosclerosis. However, the alteration of miRNA profile in EAT during atherosclerosis is still uncovered. METHODS: The miRNA expression profiles of EAT from non-coronary atherosclerosis disease (CON, n = 3) and coronary atherosclerosis disease (CAD, n = 5) patients was performed to detect the differentially expressed miRNA. Then the expression levels of miRNA in other CON (n = 5) and CAD (n = 16) samples were confirmed by realtime-PCR. miR-200b-3p mimic was used to overexpress the miRNA in HUVECs. The apoptosis of HUVECs cells was induced by H(2)O(2) and ox-LDL, and detected by Annexin V/PI Staining, Caspase 3/7 activity and the expression of BCL-2 and BAX. RESULTS: 250 miRNAs were differentially expressed in EAT from CAD patients, which were associated with metabolism, extracellular matrix and inflammation process. Among the top 20 up-regulated miRNAs, the expression levels of miR-200 family members (hsa-miR-200b/c-3p, miR-141-3p and miR-429), which were rich in endothelial cells, were increased in EAT from CAD patients significantly. Upregulation of miR-200 family members was dependent on the oxidative stress. The overexpression of miR-200b-3p could promote endothelial cells apoptosis under oxidative stress by targeting HDAC4 inhibition. CONCLUSIONS: Our study suggests that EAT derived miR-200b-3p promoted oxidative stress induced endothelial cells damage by targeting HDAC4, which may provide a new and promising therapeutic target for AS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-01980-0.
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spelling pubmed-80427262021-04-14 MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis Zhang, Fan Cheng, Naixuan Du, Jie Zhang, Haibo Zhang, Congcong BMC Cardiovasc Disord Research Article BACKGROUND: Epicardial adipose tissue (EAT) shares the same microcirculation with coronary arteries through coronary arteries branches, and contributes to the development of atherosclerosis. MicroRNAs (miRNAs) are involved in the formation of atherosclerosis. However, the alteration of miRNA profile in EAT during atherosclerosis is still uncovered. METHODS: The miRNA expression profiles of EAT from non-coronary atherosclerosis disease (CON, n = 3) and coronary atherosclerosis disease (CAD, n = 5) patients was performed to detect the differentially expressed miRNA. Then the expression levels of miRNA in other CON (n = 5) and CAD (n = 16) samples were confirmed by realtime-PCR. miR-200b-3p mimic was used to overexpress the miRNA in HUVECs. The apoptosis of HUVECs cells was induced by H(2)O(2) and ox-LDL, and detected by Annexin V/PI Staining, Caspase 3/7 activity and the expression of BCL-2 and BAX. RESULTS: 250 miRNAs were differentially expressed in EAT from CAD patients, which were associated with metabolism, extracellular matrix and inflammation process. Among the top 20 up-regulated miRNAs, the expression levels of miR-200 family members (hsa-miR-200b/c-3p, miR-141-3p and miR-429), which were rich in endothelial cells, were increased in EAT from CAD patients significantly. Upregulation of miR-200 family members was dependent on the oxidative stress. The overexpression of miR-200b-3p could promote endothelial cells apoptosis under oxidative stress by targeting HDAC4 inhibition. CONCLUSIONS: Our study suggests that EAT derived miR-200b-3p promoted oxidative stress induced endothelial cells damage by targeting HDAC4, which may provide a new and promising therapeutic target for AS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-01980-0. BioMed Central 2021-04-12 /pmc/articles/PMC8042726/ /pubmed/33845782 http://dx.doi.org/10.1186/s12872-021-01980-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Zhang, Fan
Cheng, Naixuan
Du, Jie
Zhang, Haibo
Zhang, Congcong
MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis
title MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis
title_full MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis
title_fullStr MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis
title_full_unstemmed MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis
title_short MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis
title_sort microrna-200b-3p promotes endothelial cell apoptosis by targeting hdac4 in atherosclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042726/
https://www.ncbi.nlm.nih.gov/pubmed/33845782
http://dx.doi.org/10.1186/s12872-021-01980-0
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