Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP
You ZHOU1
Man-Yun LONG1
Zhi-Qing CHEN1
Jun-Wen HUANG1
Zhen-Bai QIN1
Lang LI2
1.Department of Cardiology,the First Affiliated Hospital of Guangxi Medical University,Nanning,China2.Department of Cardiology,the First Affiliated Hospital of Guangxi Medical University,Nanning,China;Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention,Nanning,China
摘要：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 poly-merase 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 im-proved 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 myocar-dial 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 ox-idative stress and inflammation through directly targeting XIAP.
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论文发表日期：2021-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 426-439 )