MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in context
Background: Atherosclerosis is a hyperlipidemia-induced condition affecting the arterial wall that damages healthy endothelial cell (EC) function, leading to enhanced risk of atherothrombotic events. Certain microRNAs regulate EC dysfunction in response to hyperlipidemia and may be suitable therapeu...
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doaj-67837713f5e34e1f8e2ff4aeec9b5a5e2020-11-25T02:03:00ZengElsevierEBioMedicine2352-39642019-02-0140685694MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in contextRongzhong Huang0Zicheng Hu1Yu Cao2Hongrong Li3Hong Zhang4Wenhua Su5Yu Xu6Liwen Liang7N.D. Melgiri8Lihong Jiang9Department of Cardiothoracic Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan Province, ChinaDepartment of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, ChinaDepartment of Cardiothoracic Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan Province, ChinaDepartment of Cardiothoracic Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan Province, ChinaDepartment of Cardiology, The First People's Hospital of Yunnan Province, Kunming, Yunnan Province, ChinaDepartment of Cardiology, The First People's Hospital of Yunnan Province, Kunming, Yunnan Province, ChinaStatistical Laboratory, Chuangxu Institute of Lifescience, Chongqing, ChinaDepartment of Cardiology, The First People's Hospital of Yunnan Province, Kunming, Yunnan Province, ChinaImpactys Foundation for Biomedical Research, San Diego, CA, USADepartment of Cardiothoracic Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan Province, China; Corresponding author at: Department of Cardiothoracic Surgery, The First People's Hospital of Yunnan Province, No. 157 Jinbi Road, Kunming 650000, China.Background: Atherosclerosis is a hyperlipidemia-induced condition affecting the arterial wall that damages healthy endothelial cell (EC) function, leading to enhanced risk of atherothrombotic events. Certain microRNAs regulate EC dysfunction in response to hyperlipidemia and may be suitable therapeutic targets to combat atherosclerosis. Methods: miRNA expression in human ECs was analyzed under various conditions to identify key microRNAs. High-cholesterol diet (HCD)-fed Mir652−/−Apoe−/− (Mir652−/−) mice and matching Mir652+/+Apoe−/− (Mir652+/+) mice were subjected to carotid injury to analyze the effects of miR-652 knockdown on endothelial repair. In silico analysis followed by in vitro and in vivo experiments were applied to identify miR-652's target gene Ccnd2 and investigate the pair's effects on ECs. miR-652-5p and miR-652-3p antagomir therapies were tested in Mir652+/+ mice under normal and HCD diet to assess their effect on endothelial repair. Findings: miR-652-3p, which is upregulated in human and murine atherosclerotic plaques, suppresses expression of the endothelial repair gene Ccnd2, thereby enhancing atherosclerotic lesion formation. Post-denudation recovery of ECs was promoted in Mir652−/− mice due to enhanced EC proliferation attributable to de-repression of miR-652-3p's (but not miR-652-5p's) regulation of Ccnd2 expression. Under hyperlipidemic conditions at non-predilection sites, miR-652-3p produces anti-proliferative effects in ECs, such that Mir652−/− mice display reduced atherosclerotic progression. In contrast, neither miR-652-3p nor Ccnd2 displayed significant effects on the endothelium at predilection sites or under disturbed flow conditions. Administration of a miR-652-3p antagomir rescued the proliferation of ECs in vivo, thereby limiting atherosclerotic development. Interpretation: miR-652-3p blockade may be a potential therapeutic strategy against atherosclerosis. Keywords: Atherosclerosis, Endothelium, Cyclin D2, CCND2, miR-652http://www.sciencedirect.com/science/article/pii/S2352396419300374 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rongzhong Huang Zicheng Hu Yu Cao Hongrong Li Hong Zhang Wenhua Su Yu Xu Liwen Liang N.D. Melgiri Lihong Jiang |
spellingShingle |
Rongzhong Huang Zicheng Hu Yu Cao Hongrong Li Hong Zhang Wenhua Su Yu Xu Liwen Liang N.D. Melgiri Lihong Jiang MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in context EBioMedicine |
author_facet |
Rongzhong Huang Zicheng Hu Yu Cao Hongrong Li Hong Zhang Wenhua Su Yu Xu Liwen Liang N.D. Melgiri Lihong Jiang |
author_sort |
Rongzhong Huang |
title |
MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in context |
title_short |
MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in context |
title_full |
MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in context |
title_fullStr |
MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in context |
title_full_unstemmed |
MiR-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting Cyclin D2 expressionResearch in context |
title_sort |
mir-652-3p inhibition enhances endothelial repair and reduces atherosclerosis by promoting cyclin d2 expressionresearch in context |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-02-01 |
description |
Background: Atherosclerosis is a hyperlipidemia-induced condition affecting the arterial wall that damages healthy endothelial cell (EC) function, leading to enhanced risk of atherothrombotic events. Certain microRNAs regulate EC dysfunction in response to hyperlipidemia and may be suitable therapeutic targets to combat atherosclerosis. Methods: miRNA expression in human ECs was analyzed under various conditions to identify key microRNAs. High-cholesterol diet (HCD)-fed Mir652−/−Apoe−/− (Mir652−/−) mice and matching Mir652+/+Apoe−/− (Mir652+/+) mice were subjected to carotid injury to analyze the effects of miR-652 knockdown on endothelial repair. In silico analysis followed by in vitro and in vivo experiments were applied to identify miR-652's target gene Ccnd2 and investigate the pair's effects on ECs. miR-652-5p and miR-652-3p antagomir therapies were tested in Mir652+/+ mice under normal and HCD diet to assess their effect on endothelial repair. Findings: miR-652-3p, which is upregulated in human and murine atherosclerotic plaques, suppresses expression of the endothelial repair gene Ccnd2, thereby enhancing atherosclerotic lesion formation. Post-denudation recovery of ECs was promoted in Mir652−/− mice due to enhanced EC proliferation attributable to de-repression of miR-652-3p's (but not miR-652-5p's) regulation of Ccnd2 expression. Under hyperlipidemic conditions at non-predilection sites, miR-652-3p produces anti-proliferative effects in ECs, such that Mir652−/− mice display reduced atherosclerotic progression. In contrast, neither miR-652-3p nor Ccnd2 displayed significant effects on the endothelium at predilection sites or under disturbed flow conditions. Administration of a miR-652-3p antagomir rescued the proliferation of ECs in vivo, thereby limiting atherosclerotic development. Interpretation: miR-652-3p blockade may be a potential therapeutic strategy against atherosclerosis. Keywords: Atherosclerosis, Endothelium, Cyclin D2, CCND2, miR-652 |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419300374 |
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