本文采用的英格恩产品: 增强型ECL发光液, 超敏ECL发光液

MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury.

Liu RR¹, Li J², Gong JY¹, Kuang F³, Liu JY⁴, Zhang YS¹, Ma QL¹, Song CJ¹, Truax AD⁵, Gao F², Yang K¹, Jin BQ¹, Chen LH⁶.

Author information

1Department of Immunology, Fourth Military Medical University, Xi’an, People’s Republic of China;2Department of Physiology, Fourth Military Medical University, Xi’an, People’s Republic of China;3Department of Neurobiology, Fourth Military Medical University, Xi’an, People’s Republic of China;4Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; and.5Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.6Department of Immunology, Fourth Military Medical University, Xi’an, People’s Republic of China; chenlh@fmmu.edu.cn.

Abstract

A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM-1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-α for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR-141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b(+) cells and F4/80(+) macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR-141 may constitute a new therapeutic target in the setting of ischemic heart disease.

KEYWORDS:

HUVEC; ICAM-1; ischemic reperfusion injury; miR-141; myocardial enzyme