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

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.

• Authors: You Zhou, Man-Yun Long, Zhi-Qing Chen, Jun-Wen Huang, Zhen-Bai Qin, Lang Li
• Journal: Journal of geriatric cardiology : JGC (J Geriatr Cardiol) Vol. 18 Issue 6 Pg. 426-439 (Jun 28 2021) ISSN: 1671-5411 [Print] China
• PMID: 34220972 (Publication Type: Journal Article)
• Copyright: Copyright and License information: Journal of Geriatric Cardiology 2021.