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© 2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Aims

Long non‐coding RNA HOXA11‐AS participated in heart disease. In this study, we aim to evaluate the potential roles of HOXA11‐AS in atherosclerosis and its underlying mechanisms.

Methods and results

The expression levels of HOXA11‐AS in ox‐LDL‐treated HUVECs and arch tissues of high‐fat diet‐fed ApoE−/− mice (n = 10) were assessed by qRT‐PCR. The effects of HOXA11‐AS knockdown on the development of atherosclerosis were evaluated using in vitro and in vivo models. Luciferase reporter and RNA immunoprecipitation (RIP) assays verified the potential relationships between HOXA11‐AS or ROCK1 and miR‐515‐5p. The interactive roles between HOXA11‐AS and miR‐515‐5p and between miR‐515‐5p and ROCK1 were further characterized in ox‐LDL‐treated HUVECs. Our data showed that HOXA11‐AS was significantly up‐regulated (P < 0.001), whereas miR‐515‐5p was dramatically down‐regulated in AS mice tissues (P < 0.001) and ox‐LDL‐treated HUVECs (P < 0.01). Ox‐LDL could induce endothelial injuries by inhibiting cell proliferation (P < 0.001) and SOD synthesis (P < 0.001), promoting apoptosis (P < 0.01), ROS (P < 0.001), and MDA production (P < 0.001), increasing Bax (P < 0.001) and cleaved Caspase‐3 (P < 0.001), and decreasing Bcl‐2 (P < 0.001) and phosphorylated eNOS (P < 0.01). HOXA11‐AS knockdown attenuated endothelial injuries via increasing eNOS phosphorylation. Luciferase assay and RIP results confirmed that miR‐515‐5p is directly bound to HOXA11‐AS and ROCK1. HOXA11‐AS promoted ox‐LDL‐induced HUVECs injury by directly inhibiting miR‐515‐5p from increasing ROCK1 expression and subsequently decreasing the expression and phosphorylation of eNOS. MiR‐515‐5p mimics could partially reverse the effects of HOXA11‐AS knockdown.

Conclusions

HOXA11‐AS contributed to atherosclerotic injuries by directly regulating the miR‐515‐5p/ROCK1 axis. This study provided new evidence that HOXA11‐AS might be a candidate for atherosclerosis therapy.

Details

Title
LncRNA HOXA11‐AS promotes vascular endothelial cell injury in atherosclerosis by regulating the miR‐515‐5p/ROCK1 axis
Author
Gao, Feng 1 ; Wang, Xiao‐Chen 1 ; Luo, Zhi‐Dan 2 ; Hu, Guang‐Quan 1 ; Ma, Meng‐Qing 3 ; Liang, Yi 4 ; Xu, Bang‐Long 1 ; Lin, Xian‐He 3   VIAFID ORCID Logo 

 Department of Cardiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China 
 Department of Geriatrics, Chongqing People's Hospital, Chongqing, China 
 Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China 
 Houston Methodist Research Institute, Center for Cardiovascular Regeneration, Houston, TX, USA 
Pages
2259-2271
Section
Original Articles
Publication year
2022
Publication date
Aug 1, 2022
Publisher
John Wiley & Sons, Inc.
e-ISSN
20555822
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2690638698
Copyright
© 2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.