AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Journal of Geriatric Cardiology Article
View PDF
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

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 LI1,2( )
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

*The authors contributed equally to this manuscript

Show Author Information

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.

References

[1]

Erbel R, Heusch G. Coronary microembolization. J Am Coll Cardiol 2000; 36: 22−24.
DOI Google Scholar
[2]

Salem SA, Haji S, Garg N, et al. Occlusion of right coronary artery by microembolization caused by excessive diagnostic catheter manipulation. Ann Transl Med 2018; 6: 20.
DOI Google Scholar
[3]

Heusch G, Skyschally A, Kleinbongard P. Coronary microembolization and microvascular dysfunction. Int J Cardiol 2018; 258: 17−23.
DOI Google Scholar
[4]

Wang Y, Zhao HW, Wang CF, et al. Incidence, predictors, and prognosis of coronary slow-flow and no-reflow phenomenon in patients with chronic total occlusion who underwent percutaneous coronary intervention. Ther Clin Risk Manag 2020; 16: 95−101.
DOI Google Scholar
[5]

Kalyoncuoglu M, Biter Hİ, Ozturk S, et al. Predictive accuracy of lymphocyte-to-monocyte ratio and monocyte-to-high-density-lipoprotein-cholesterol ratio in determining the slow flow/no-reflow phenomenon in patients with non-ST-elevated myocardial infarction. Coron Artery Dis 2020; 31: 518−526.
DOI Google Scholar
[6]

Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007; 356: 830−840.
DOI Google Scholar
[7]

Nakanishi K, Daimon M. Coronary slow flow and subclinical left ventricular dysfunction. Int Heart J 2019; 60: 495−496.
DOI Google Scholar
[8]

Heusch G. The regional myocardial flow-function relationship: a framework for an understanding of acute ischemia, hibernation, stunning and coronary microembolization. 1980. Circ Res 2013; 112: 1535−1537.
DOI Google Scholar
[9]

Chen ZW, Qian JY, Ma JY, et al. TNF-α-induced cardiomyocyte apoptosis contributes to cardiac dysfunction after coronary microembolization in mini-pigs. J Cell Mol Med 2014; 18: 1953−1963.
DOI Google Scholar
[10]

Chen A, Chen Z, Zhou Y, et al. Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation. Cell Death Dis 2021; 12: 78.
DOI Google Scholar
[11]

Su Q, Lv X, Ye Z. Ligustrazine attenuates myocardial injury induced by coronary microembolization in rats by activating the PI3K/Akt pathway. Oxid Med Cell Longev 2019; 2019: 6791457.
DOI Google Scholar
[12]

Zhu L, Li N, Sun L, et al. Non-coding RNAs: the key detectors and regulators in cardiovascular disease. Genomics 2021; 113: 1233−1246.
DOI Google Scholar
[13]

Arabian M, Mirzadeh Azad F, Maleki M, et al. Insights into role of microRNAs in cardiac development, cardiac diseases, and developing novel therapies. Iran J Basic Med Sci 2020; 23: 961−969.
DOI Google Scholar
[14]

Zhou H, Ni WJ, Meng XM, et al. MicroRNAs as regulators of immune and inflammatory responses: potential therapeutic targets in diabetic nephropathy. Front Cell Dev Biol 2021; 8: 618536.
DOI Google Scholar
[15]

Colpaert RMW, Calore M. Epigenetics and microRNAs in cardiovascular diseases. Genomics 2021; 113: 540−551.
DOI Google Scholar
[16]

Ye H, Xu G, Zhang D, et al. The protective effects of the miR-129-5p/keap-1/Nrf2 axis on Ang II-induced cardiomyocyte hypertrophy. Ann Transl Med 2021; 9: 154.
DOI Google Scholar
[17]
Qu Y, Zhang J, Zhang J, et al. MiR-708-3p alleviates inflammation and myocardial injury after myocardial infarction by suppressing ADAM17 expression. Inflammation. Published Online First: 25 January 2021. DOI: 10.1007/s10753-020-01404-9.
[18]

Su Q, Lv X, Ye Z, et al. The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1. Cell Death Dis 2019; 10: 61.
DOI Google Scholar
[19]

Zhu HH, Wang XT, Sun YH, et al. MicroRNA-486-5p targeting PTEN protects against coronary microembolization-induced cardiomyocyte apoptosis in rats by activating the PI3K/AKT pathway. Eur J Pharmacol 2019; 855: 244−251.
DOI Google Scholar
[20]

Sun X, Sit A, Feinberg MW. Role of miR-181 family in regulating vascular inflammation and immunity. Trends Cardiovasc Med 2014; 24: 105−112.
DOI Google Scholar
[21]

Sun YH, Su Q, Li L, et al. Expression of p53 in myocardium following coronary microembolization in rats and its significance. J Geriatr Cardiol 2017; 14: 292−300.
DOI Google Scholar
[22]

Heusch G. The coronary circulation as a target of cardioprotection. Circ Res 2016; 118: 1643−1658.
DOI Google Scholar
[23]

Malyar NM, Lerman LO, Gössl M, et al. Relation of nonperfused myocardial volume and surface area to left ventricular performance in coronary microembolization. Circulation 2004; 110: 1946−1952.
DOI Google Scholar
[24]

Dörge H, Schulz R, Belosjorow S, et al. Coronary microembolization: the role of TNF-alpha in contractile dysfunction. J Mol Cell Cardiol 2002; 34: 51−62.
DOI Google Scholar
[25]

Li S, Zhong S, Zeng K, et al. Blockade of NF-kappaB by pyrrolidine dithiocarbamate attenuates myocardial inflammatory response and ventricular dysfunction following coronary microembolization induced by homologous microthrombi in rats. Basic Res Cardiol 2010; 105: 139−150.
DOI Google Scholar
[26]

Su Q, Li L, Sun Y, et al. Effects of the TLR4/Myd88/NF-kappaB signaling pathway on NLRP3 inflammasome in coronary microembolization-induced myocardial injury. Cell Physiol Biochem 2018; 47: 1497−1508.
DOI Google Scholar
[27]

Ambros V. MicroRNAs: tiny regulators with great potential. Cell 2001; 107: 823−826.
DOI Google Scholar
[28]

Ke XS, Liu CM, Liu DP, et al. MicroRNAs: key participants in gene regulatory networks. Curr Opin Chem Biol 2003; 7: 516−523.
DOI Google Scholar
[29]

Kong B, Qin Z, Ye Z, et al. MicroRNA-26a-5p affects myocardial injury induced by coronary microembolization by modulating HMGA1. J Cell Biochem 2019; 120: 10756−10766.
DOI Google Scholar
[30]

Qin S, Yang C, Zhang B, et al. XIAP inhibits mature Smac-induced apoptosis by degrading it through ubiquitination in NSCLC. Int J Oncol 2016; 49: 1289−1296.
DOI Google Scholar
[31]

Estornes Y, Bertrand MJM. IAPs, regulators of innate immunity and inflammation. Semin Cell Dev Biol 2015; 39: 106−114.
DOI Google Scholar
[32]

Lu M, Qin X, Yao J, et al. MiR-134-5p targeting XIAP modulates oxidative stress and apoptosis in cardiomyocytes under hypoxia/reperfusion-induced injury. IUBMB Life 2020; 72: 2154−2166.
DOI Google Scholar
[33]

Zhao R, Yu Q, Hou L, et al. Cadmium induces mitochondrial ROS inactivation of XIAP pathway leading to apoptosis in neuronal cells. Int J Biochem Cell Biol 2020; 121: 105715.
DOI Google Scholar
[34]

Zilu S, Qian H, Haibin W, et al. Effects of XIAP on high fat diet-induced hepatic steatosis: a mechanism involving NLRP3 inflammasome and oxidative stress. Aging 2019; 11: 12177−12201.
DOI Google Scholar
[35]

Zheng J, Long M, Qin Z, et al. Nicorandil inhibits cardiomyocyte apoptosis and improves cardiac function by suppressing the HtrA2/XIAP/PARP signaling after coronary microembolization in rats. Pharmacol Res Perspect 2021; 9: e00699.
DOI Google Scholar
Journal of Geriatric Cardiology
Volume 18 Issue 6,
June 2021
Pages 426-439
DOI: 10.11909/j.issn.1671-5411.2021.06.007
Cite this article:
ZHOU Y, LONG M-Y, CHEN Z-Q, et al. Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP. Journal of Geriatric Cardiology, 2021, 18(6): 426-439. https://doi.org/10.11909/j.issn.1671-5411.2021.06.007

531

Views

25

Downloads

0

Crossref

16

Web of Science

12

Scopus

0

CSCD
Published: 28 June 2021
© 2021 JGC All rights reserved
Return