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

BMC Cardiovascular Disorders

Zhanhu Li¹  Yong Li¹  Yuan Li¹  Hongbo Zhang¹  Shuai Liu¹  Xiaoju Yan¹ 

[1] Department of Cardiology, Harrision International Peace Hospital, No. 180 Renmin East Road, 053000, Hengshui, Hebei, People’s Republic of China;

关键词: Myocardium ischemia reperfusion injury;    microRNA-130a-5p;    HMGB2;    NF-κb pathway;    Oxidative stress;    Mitochondrial disorder;   

DOI  :  10.1186/s12872-020-01742-4

来源: Springer

【 摘 要 】

BackgroundMyocardial 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.MethodsMIRI 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.ResultsDisrupted 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.ConclusionOur 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.

【 授权许可】

CC BY