Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP

You ZHOU; Man-Yun LONG; Zhi-Qing CHEN; Jun-Wen HUANG; Zhen-Bai QIN; Lang LI

doi:10.11909/j.issn.1671-5411.2021.06.007

Volume 18 Issue 6

Jun. 2021

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Article Navigation > Journal of Geriatric Cardiology > 2021 > 18(6): 426-439

Please cite this article as: ZHOU Y, LONG MY, CHEN ZQ, HUANG JW, QIN ZB, LI L. Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP. J Geriatr Cardiol 2021; 18(6): 426−439. DOI: 10.11909/j.issn.1671-5411.2021.06.007

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Please cite this article as: ZHOU Y, LONG MY, CHEN ZQ, HUANG JW, QIN ZB, LI L. Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP. J Geriatr Cardiol 2021; 18(6): 426−439. DOI: 10.11909/j.issn.1671-5411.2021.06.007

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Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP

doi: 10.11909/j.issn.1671-5411.2021.06.007

You ZHOU^{1, *},
Man-Yun LONG^{1, *},
Zhi-Qing CHEN¹,
Jun-Wen HUANG¹,
Zhen-Bai QIN¹,
Lang LI^{1, 2
,
,}

1.
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
2.
Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, Nanning, China

^*The authors contributed equally to this manuscript

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Corresponding author: drlilang1968@126.com
Available Online: 2021-05-28
Publish Date: 2021-06-22

Abstract

Abstract

BACKGROUND Coronary microembolization (CME) is a complicated problem that commonly arises in the context of coronary angioplasty. MicroRNAs play crucial roles in cardiovascular diseases. However, the role and mechanism of miR-181a-5p in CME-induced myocardial injury remains unclear. METHODS We established CME rat models. Cardiac function was detected by echocardiography. Haematoxylin-basic fuchsin-picric acid staining was used to measure micro-infarction size. Serum samples and cell culture supernatants were evaluated via enzyme-linked immunosorbent assay. Cellular reactive oxygen species were determined by dichloro-dihydro-fluorescein diacetate assay, and the other oxidative stress related parameters were assayed by spectrophotometry. The dual-luciferase reporter (DLR) assay and RNA pulldown were conducted to validate the association between miR-181a-5p and X-linked inhibitor of apoptosis protein (XIAP). The expression of miR-181a-5p and XIAP mRNA were determined by quantitative reverse transcription polymerase chain reaction. Proteins were evaluated via immunoblotting. The viability of the cell was evaluated via cell counting kit-8 assay. RESULTS The miR-181a-5p level was significantly increased in CME myocardial tissues. Downregulation of miR-181a-5p improved CME-induced cardiac dysfunction and alleviated myocardial oxidative stress and inflammatory injury, whereas miR-181a-5p exhibited the opposite effects. Then, the DLR assay and RNA pulldown results revealed that miR-181a-5p directly targeting on XIAP. The XIAP level was found to be remarkably decreased after CME. XIAP overexpression attenuated CME-induced myocardial oxidative stress and inflammatory injury. Finally, in vitro rescue experiments revealed that knockdown of XIAP could abolish the protective effects of miR-181a-5p knockdown on hypoxia-induced cardiomyocyte oxidative stress and inflammatory injury. CONCLUSIONS Downregulation of miR-181a-5p alleviates CME-induced myocardial damage by suppressing myocardial oxidative stress and inflammation through directly targeting XIAP.

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