title: MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury.
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.
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Rong Rong
authors.initials: RR
authors.lastname: Liu
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Jiu Yu
authors.initials: JY
authors.lastname: Gong
authors.affiliation: Department of Neurobiology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Fang
authors.initials: F
authors.lastname: Kuang
authors.affiliation: Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China; and.
authors.forename: Jia Yun
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Yu Si
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Qian Li
authors.initials: QL
authors.lastname: Ma
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Chao Jun
authors.initials: CJ
authors.lastname: Song
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Agnieszka D
authors.initials: AD
authors.lastname: Truax
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China;
authors.forename: Bo Quan
authors.initials: BQ
authors.lastname: Jin
authors.affiliation: Department of Immunology, Fourth Military Medical University, Xi'an, People's Republic of China; chenlh@fmmu.edu.cn.
authors.forename: Li Hua
authors.initials: LH
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002448:Cell Adhesion; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; C573420:ICAM1 protein, human; C090509:Icam1 protein, mouse; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; C543718:Mirn141 microRNA, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1
keywords: HUVEC; ICAM-1; ischemic reperfusion injury; miR-141; myocardial enzyme