Am J Physiol Heart Circ Physiol. 2015 Oct;309(8):H1303-13. doi: 10.1152/ajpheart.00290.2015. Epub 2015 Sep 14.

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

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