دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury.
المؤلفون: Rong Rong Liu, Jun Li, Jiu Yu Gong, Fang Kuang, Jia Yun Liu, Yu Si Zhang, Qian Li Ma, Chao jun Song, Truax, Agnieszka D., Feng Gao, Kun Yang, Bo Quan Jin, Li Hua Chen
المصدر: American Journal of Physiology: Heart & Circulatory Physiology; Oct2015, Vol. 309 Issue 8, pH1303-H1313, 11p
مصطلحات موضوعية: MICRORNA, ENDOTHELIUM, ISCHEMIA, REPERFUSION injury, REPERFUSION
مستخلص: 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 down regulated in the ECs challenged with TNF-a 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 CDllb+ 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. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:03636135
DOI:10.1152/ajpheart.00290.2015