microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. Ho...

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Main Authors: Yong Li, Hongbo Zhang, Zhanhu Li, Xiaoju Yan, Yuan Li, Shuai Liu
Format: Article
Language:English
Published: BMC 2021-03-01
Series:BMC Cardiovascular Disorders
Subjects:
Online Access:https://doi.org/10.1186/s12872-020-01742-4
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author Yong Li
Hongbo Zhang
Zhanhu Li
Xiaoju Yan
Yuan Li
Shuai Liu
author_facet Yong Li
Hongbo Zhang
Zhanhu Li
Xiaoju Yan
Yuan Li
Shuai Liu
author_sort Yong Li
collection DOAJ
description Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.
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spelling doaj.art-ea7654dccbeb488b80aeb8d7d20966932022-12-21T22:42:05ZengBMCBMC Cardiovascular Disorders1471-22612021-03-0121111110.1186/s12872-020-01742-4microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axisYong Li0Hongbo Zhang1Zhanhu Li2Xiaoju Yan3Yuan Li4Shuai Liu5Department of Cardiology, Harrision International Peace HospitalDepartment of Cardiology, Harrision International Peace HospitalDepartment of Cardiology, Harrision International Peace HospitalDepartment of Cardiology, Harrision International Peace HospitalDepartment of Cardiology, Harrision International Peace HospitalDepartment of Cardiology, Harrision International Peace HospitalAbstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.https://doi.org/10.1186/s12872-020-01742-4Myocardium ischemia reperfusion injurymicroRNA-130a-5pHMGB2NF-κb pathwayOxidative stressMitochondrial disorder
spellingShingle Yong Li
Hongbo Zhang
Zhanhu Li
Xiaoju Yan
Yuan Li
Shuai Liu
microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis
BMC Cardiovascular Disorders
Myocardium ischemia reperfusion injury
microRNA-130a-5p
HMGB2
NF-κb pathway
Oxidative stress
Mitochondrial disorder
title microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis
title_full microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis
title_fullStr microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis
title_full_unstemmed microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis
title_short microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis
title_sort microrna 130a 5p suppresses myocardial ischemia reperfusion injury by downregulating the hmgb2 nf κb axis
topic Myocardium ischemia reperfusion injury
microRNA-130a-5p
HMGB2
NF-κb pathway
Oxidative stress
Mitochondrial disorder
url https://doi.org/10.1186/s12872-020-01742-4
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