Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension

Arterial stiffness due to the vessel remodeling is closely linked to raised blood pressure, and its physiopathologic mechanism is still not fully understood. We here aimed to explore whether extracellular vesicle (EV) mediated intercellular communication between endothelium and smooth muscle cell co...

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Autores principales: Chen Wang, Changyang Xing, Zhelong Li, Yunnan Liu, Qiaoying Li, Yixiao Wang, Jiao Hu, Lijun Yuan, Guodong Yang
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Publicado: KeAi Communications Co., Ltd. 2022
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Acceso en línea:https://doaj.org/article/5eff8fcd88404295b32a5578e2751198
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spelling oai:doaj.org-article:5eff8fcd88404295b32a5578e27511982021-11-04T04:34:59ZBioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension2452-199X10.1016/j.bioactmat.2021.06.005https://doaj.org/article/5eff8fcd88404295b32a5578e27511982022-02-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21002887https://doaj.org/toc/2452-199XArterial stiffness due to the vessel remodeling is closely linked to raised blood pressure, and its physiopathologic mechanism is still not fully understood. We here aimed to explore whether extracellular vesicle (EV) mediated intercellular communication between endothelium and smooth muscle cell contribute to the blood vessel remodeling under hypertension. We here revealed that the arterial endothelial cells robustly secreted EV, which in turn could be circulated and/or directly taken up by the subendothelial smooth muscle cells (SMC). Under hypertension, the EV secretion increased and the miRNA profile changed significantly mainly due to the raised mechanical force and subsequent enhanced reactive oxygen species generation. Among the miRNA cargos in the EV, miR-320d/423-5p were found increased most significantly. In vivo delivery of miR-320d/423-5p mimics via engineered EV increased their expression in arterial vessels, recapitulating the phenotype in hypertension. In contrast, therapeutic delivery of miR-320d/423-5p inhibitors via engineered EV alleviated the phenotype in spontaneous hypertension rat model. Together, we have found that the injured endothelium due to the raised mechanical force in hypertension contributes to the arterial wall remodeling via the secreted EV. Our study has not only provided novel insights on the mechanism of hypertension associated blood vessel wall remodeling, but also shed light on therapeutic intervention of hypertension associated vascular diseases.Chen WangChangyang XingZhelong LiYunnan LiuQiaoying LiYixiao WangJiao HuLijun YuanGuodong YangKeAi Communications Co., Ltd.articleHypertensionExtracellular vesiclesEndothelial cellSmooth muscle cellPhenotype switchmicroRNAMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 8, Iss , Pp 494-504 (2022)
institution DOAJ
collection DOAJ
language EN
topic Hypertension
Extracellular vesicles
Endothelial cell
Smooth muscle cell
Phenotype switch
microRNA
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
spellingShingle Hypertension
Extracellular vesicles
Endothelial cell
Smooth muscle cell
Phenotype switch
microRNA
Materials of engineering and construction. Mechanics of materials
TA401-492
Biology (General)
QH301-705.5
Chen Wang
Changyang Xing
Zhelong Li
Yunnan Liu
Qiaoying Li
Yixiao Wang
Jiao Hu
Lijun Yuan
Guodong Yang
Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension
description Arterial stiffness due to the vessel remodeling is closely linked to raised blood pressure, and its physiopathologic mechanism is still not fully understood. We here aimed to explore whether extracellular vesicle (EV) mediated intercellular communication between endothelium and smooth muscle cell contribute to the blood vessel remodeling under hypertension. We here revealed that the arterial endothelial cells robustly secreted EV, which in turn could be circulated and/or directly taken up by the subendothelial smooth muscle cells (SMC). Under hypertension, the EV secretion increased and the miRNA profile changed significantly mainly due to the raised mechanical force and subsequent enhanced reactive oxygen species generation. Among the miRNA cargos in the EV, miR-320d/423-5p were found increased most significantly. In vivo delivery of miR-320d/423-5p mimics via engineered EV increased their expression in arterial vessels, recapitulating the phenotype in hypertension. In contrast, therapeutic delivery of miR-320d/423-5p inhibitors via engineered EV alleviated the phenotype in spontaneous hypertension rat model. Together, we have found that the injured endothelium due to the raised mechanical force in hypertension contributes to the arterial wall remodeling via the secreted EV. Our study has not only provided novel insights on the mechanism of hypertension associated blood vessel wall remodeling, but also shed light on therapeutic intervention of hypertension associated vascular diseases.
format article
author Chen Wang
Changyang Xing
Zhelong Li
Yunnan Liu
Qiaoying Li
Yixiao Wang
Jiao Hu
Lijun Yuan
Guodong Yang
author_facet Chen Wang
Changyang Xing
Zhelong Li
Yunnan Liu
Qiaoying Li
Yixiao Wang
Jiao Hu
Lijun Yuan
Guodong Yang
author_sort Chen Wang
title Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension
title_short Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension
title_full Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension
title_fullStr Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension
title_full_unstemmed Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension
title_sort bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension
publisher KeAi Communications Co., Ltd.
publishDate 2022
url https://doaj.org/article/5eff8fcd88404295b32a5578e2751198
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AT guodongyang bioinspiredtherapeuticplatformbasedonextracellularvesiclesforpreventionofarterialwallremodelinginhypertension
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