MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression
Proliferation of vascular smooth muscle cells (VSMCs) plays crucial roles in vascular remodelling and stiffening in hypertension. Vascular adventitial fibroblasts are a key regulator of vascular wall function and structure. This study is designed to investigate the roles of adventitial fibroblasts-d...
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2020-01-01
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Online Access: | http://dx.doi.org/10.1080/20013078.2019.1698795 |
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doaj-a70e858884c54f60a6b5172fa29c0e092020-11-25T04:05:23ZengTaylor & Francis GroupJournal of Extracellular Vesicles2001-30782020-01-019110.1080/20013078.2019.16987951698795MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expressionXing-Sheng Ren0Ying Tong1Yun Qiu2Chao Ye3Nan Wu4Xiao-Qing Xiong5Jue-Jin Wang6Ying Han7Ye-Bo Zhou8Feng Zhang9Hai-Jian Sun10Xing-Ya Gao11Qi Chen12Yue-Hua Li13Yu-Ming Kang14Guo-Qing Zhu15Nanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityCardiovascular Research Center, Xi’an Jiaotong University School of MedicineNanjing Medical UniversityProliferation of vascular smooth muscle cells (VSMCs) plays crucial roles in vascular remodelling and stiffening in hypertension. Vascular adventitial fibroblasts are a key regulator of vascular wall function and structure. This study is designed to investigate the roles of adventitial fibroblasts-derived extracellular vesicles (EVs) in VSMC proliferation and vascular remodelling in normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR), an animal model of human essential hypertension. EVs were isolated from aortic adventitial fibroblasts of WKY (WKY-EVs) and SHR (SHR-EVs). Compared with WKY-EVs, miR155-5p content was reduced, while angiotensin-converting enzyme (ACE) content was increased in SHR-EVs. WKY-EVs inhibited VSMC proliferation of SHR, which was prevented by miR155-5p inhibitor. SHR-EVs promoted VSMC proliferation of both strains, which was enhanced by miR155-5p inhibitor, but abolished by captopril or losartan. Dual luciferase reporter assay showed that ACE was a target gene of miR155-5p. MiR155-5p mimic or overexpression inhibited VSMC proliferation and ACE upregulation of SHR. WKY-EVs reduced ACE mRNA and protein expressions while SHR-EVs only increased ACE protein level in VSMCs of both strains. However, the SHR-EVs-derived from the ACE knockdown-treated adventitial fibroblasts lost the roles in promoting VSMC proliferation and ACE upregulation. Systemic miR155-5p overexpression reduced vascular ACE, angiotensin II and proliferating cell nuclear antigen levels, and attenuated hypertension and vascular remodelling in SHR. Repetitive intravenous injection of SHR-EVs increased blood pressure and vascular ACE contents, and promoted vascular remodelling in both strains, while WKY-EVs reduced vascular ACE contents and attenuated hypertension and vascular remodelling in SHR. We concluded that WKY-EVs-mediated miR155-5p transfer attenuates VSMC proliferation and vascular remodelling in SHR via suppressing ACE expression, while SHR-EVs-mediated ACE transfer promotes VSMC proliferation and vascular remodelling.http://dx.doi.org/10.1080/20013078.2019.1698795micrornaextracellular vesicleexosomehypertensionvascular smooth muscle cellproliferationangiotensin converting enzyme |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xing-Sheng Ren Ying Tong Yun Qiu Chao Ye Nan Wu Xiao-Qing Xiong Jue-Jin Wang Ying Han Ye-Bo Zhou Feng Zhang Hai-Jian Sun Xing-Ya Gao Qi Chen Yue-Hua Li Yu-Ming Kang Guo-Qing Zhu |
spellingShingle |
Xing-Sheng Ren Ying Tong Yun Qiu Chao Ye Nan Wu Xiao-Qing Xiong Jue-Jin Wang Ying Han Ye-Bo Zhou Feng Zhang Hai-Jian Sun Xing-Ya Gao Qi Chen Yue-Hua Li Yu-Ming Kang Guo-Qing Zhu MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression Journal of Extracellular Vesicles microrna extracellular vesicle exosome hypertension vascular smooth muscle cell proliferation angiotensin converting enzyme |
author_facet |
Xing-Sheng Ren Ying Tong Yun Qiu Chao Ye Nan Wu Xiao-Qing Xiong Jue-Jin Wang Ying Han Ye-Bo Zhou Feng Zhang Hai-Jian Sun Xing-Ya Gao Qi Chen Yue-Hua Li Yu-Ming Kang Guo-Qing Zhu |
author_sort |
Xing-Sheng Ren |
title |
MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression |
title_short |
MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression |
title_full |
MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression |
title_fullStr |
MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression |
title_full_unstemmed |
MiR155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression |
title_sort |
mir155-5p in adventitial fibroblasts-derived extracellular vesicles inhibits vascular smooth muscle cell proliferation via suppressing angiotensin-converting enzyme expression |
publisher |
Taylor & Francis Group |
series |
Journal of Extracellular Vesicles |
issn |
2001-3078 |
publishDate |
2020-01-01 |
description |
Proliferation of vascular smooth muscle cells (VSMCs) plays crucial roles in vascular remodelling and stiffening in hypertension. Vascular adventitial fibroblasts are a key regulator of vascular wall function and structure. This study is designed to investigate the roles of adventitial fibroblasts-derived extracellular vesicles (EVs) in VSMC proliferation and vascular remodelling in normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR), an animal model of human essential hypertension. EVs were isolated from aortic adventitial fibroblasts of WKY (WKY-EVs) and SHR (SHR-EVs). Compared with WKY-EVs, miR155-5p content was reduced, while angiotensin-converting enzyme (ACE) content was increased in SHR-EVs. WKY-EVs inhibited VSMC proliferation of SHR, which was prevented by miR155-5p inhibitor. SHR-EVs promoted VSMC proliferation of both strains, which was enhanced by miR155-5p inhibitor, but abolished by captopril or losartan. Dual luciferase reporter assay showed that ACE was a target gene of miR155-5p. MiR155-5p mimic or overexpression inhibited VSMC proliferation and ACE upregulation of SHR. WKY-EVs reduced ACE mRNA and protein expressions while SHR-EVs only increased ACE protein level in VSMCs of both strains. However, the SHR-EVs-derived from the ACE knockdown-treated adventitial fibroblasts lost the roles in promoting VSMC proliferation and ACE upregulation. Systemic miR155-5p overexpression reduced vascular ACE, angiotensin II and proliferating cell nuclear antigen levels, and attenuated hypertension and vascular remodelling in SHR. Repetitive intravenous injection of SHR-EVs increased blood pressure and vascular ACE contents, and promoted vascular remodelling in both strains, while WKY-EVs reduced vascular ACE contents and attenuated hypertension and vascular remodelling in SHR. We concluded that WKY-EVs-mediated miR155-5p transfer attenuates VSMC proliferation and vascular remodelling in SHR via suppressing ACE expression, while SHR-EVs-mediated ACE transfer promotes VSMC proliferation and vascular remodelling. |
topic |
microrna extracellular vesicle exosome hypertension vascular smooth muscle cell proliferation angiotensin converting enzyme |
url |
http://dx.doi.org/10.1080/20013078.2019.1698795 |
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