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MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells

Hypertension is a major risk factor for the development of atherosclerosis. Increased carotid intima-media thickness (CIMT) is generally considered as an early marker of atherosclerosis. Recently, circulating miRNAs have been implicated both as sensitive biomarkers and key regulators in the developm...

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Detalles Bibliográficos
Autores principales: Zhao, Xin, Yi, Yaping, Meng, Chao, Fang, Ningyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328933/
https://www.ncbi.nlm.nih.gov/pubmed/30333257
http://dx.doi.org/10.1042/BSR20181218
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author Zhao, Xin
Yi, Yaping
Meng, Chao
Fang, Ningyuan
author_facet Zhao, Xin
Yi, Yaping
Meng, Chao
Fang, Ningyuan
author_sort Zhao, Xin
collection PubMed
description Hypertension is a major risk factor for the development of atherosclerosis. Increased carotid intima-media thickness (CIMT) is generally considered as an early marker of atherosclerosis. Recently, circulating miRNAs have been implicated both as sensitive biomarkers and key regulators in the development of atherosclerosis. However, the biological functions and molecular regulatory mechanisms for miR-575 on angiogenesis remain unknown. In our study, we first identified up-regulation of circulating miR-575 in plasma of essential hypertensive patients with increased CIMT (iCIMT) compared with those patients with normal CIMT (nCIMT). Furthermore, the overexpression of miR-575 in human umbilical vein endothelial cells (HUVECs) by its mimics significantly inhibited migration and proliferation as well as induction of apoptosis of HUVECs. Inhibition of miR-575 performed the reverse effects of HUVECs. We further suggested Rab5B was the downstream target of miR-575 and knockdown of Rab5B significantly inhibited migration and proliferation of HUVECs. Overexpression of Rab5B largely rescued the miR-575-mediated impairment of angiogenesis processes including: cell proliferation, migration, and apoptosis as well as activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK) signaling. Therefore, our results uncover a novel role of miR-575 in endothelial cells, implying a potential biomarker and clinical target for atherosclerosis in hypertensive patients.
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spelling pubmed-63289332019-01-18 MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells Zhao, Xin Yi, Yaping Meng, Chao Fang, Ningyuan Biosci Rep Research Articles Hypertension is a major risk factor for the development of atherosclerosis. Increased carotid intima-media thickness (CIMT) is generally considered as an early marker of atherosclerosis. Recently, circulating miRNAs have been implicated both as sensitive biomarkers and key regulators in the development of atherosclerosis. However, the biological functions and molecular regulatory mechanisms for miR-575 on angiogenesis remain unknown. In our study, we first identified up-regulation of circulating miR-575 in plasma of essential hypertensive patients with increased CIMT (iCIMT) compared with those patients with normal CIMT (nCIMT). Furthermore, the overexpression of miR-575 in human umbilical vein endothelial cells (HUVECs) by its mimics significantly inhibited migration and proliferation as well as induction of apoptosis of HUVECs. Inhibition of miR-575 performed the reverse effects of HUVECs. We further suggested Rab5B was the downstream target of miR-575 and knockdown of Rab5B significantly inhibited migration and proliferation of HUVECs. Overexpression of Rab5B largely rescued the miR-575-mediated impairment of angiogenesis processes including: cell proliferation, migration, and apoptosis as well as activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK) signaling. Therefore, our results uncover a novel role of miR-575 in endothelial cells, implying a potential biomarker and clinical target for atherosclerosis in hypertensive patients. Portland Press Ltd. 2019-01-08 /pmc/articles/PMC6328933/ /pubmed/30333257 http://dx.doi.org/10.1042/BSR20181218 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Zhao, Xin
Yi, Yaping
Meng, Chao
Fang, Ningyuan
MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells
title MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells
title_full MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells
title_fullStr MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells
title_full_unstemmed MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells
title_short MiRNA-575 suppresses angiogenesis by targeting Rab5-MEK-ERK pathway in endothelial cells
title_sort mirna-575 suppresses angiogenesis by targeting rab5-mek-erk pathway in endothelial cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328933/
https://www.ncbi.nlm.nih.gov/pubmed/30333257
http://dx.doi.org/10.1042/BSR20181218
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