[1]何芮,丁畅,何丽,等.miR-1改善异丙肾上腺素诱导的小鼠心力衰竭[J].第三军医大学学报,2019,41(14):1357-1364.
 HE Rui,DING Chang,HE Li,et al.Intravenous delivery of a microRNA-1 agomir improves isoproterenol-induced heart failure in mice[J].J Third Mil Med Univ,2019,41(14):1357-1364.
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miR-1改善异丙肾上腺素诱导的小鼠心力衰竭(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第14期
页码:
1357-1364
栏目:
基础医学
出版日期:
2019-07-30

文章信息/Info

Title:
Intravenous delivery of a microRNA-1 agomir improves isoproterenol-induced heart failure in mice
作者:
何芮丁畅何丽石毓君苏立
重庆医科大学附属第二医院心血管内科;四川大学华西医院病理研究室
Author(s):
HE Rui DING Chang HE Li SHI Yujun SU Li

Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400014; Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041,  China

关键词:
miR-1异丙肾上腺素心力衰竭NT-proBNP线粒体钙单向转运蛋白
Keywords:
microRNA-1 isoproterenol heart failure NT-proBNP mitochondrial calcium uniporter
分类号:
Q522.2;R-332;R541.605
文献标志码:
A
摘要:

目的 探讨miR-1对异丙肾上腺素(isoproterenol, ISO)诱导的小鼠心力衰竭的作用。方法 60 mg/kg ISO连续腹腔注射28 d建立C57BL/6小鼠心力衰竭模型,生理盐水连续腹腔注射28 d作为对照,第29天行超声心动图评估心力衰竭模型。模型建立后对miR-1治疗组、模型组和对照组分别予以agomir-1、agomir对照试剂和生理盐水尾静脉注射,2次/周,第7天再次行超声心动图检查,取小鼠心脏组织行HE染色、天狼星红染色、Masson三色染色、WGA及Ki67免疫荧光染色。酶联免疫法检测血清NT-proBNP水平。Western blot检测与免疫组化染色评估miR-1靶基因线粒体钙单向转运蛋白(mitochondrial calcium uniporter,MCU)的表达。结果 ISO连续腹腔注射28 d成功建立小鼠心力衰竭模型。超声心动图检测结果显示,miR-1治疗组小鼠心功能较模型组明显改善(P<0.05);组织学观察结果显示,miR-1治疗组小鼠心肌排列紊乱、心肌纤维化、心肌细胞肥大及细胞增殖等心室重构情况较模型组明显改善。miR-1治疗组血清NT-proBNP水平较模型组明显下降(P<0.05),但仍高于对照组(P<0.05)。Western blot检测与免疫组化结果显示,miR-1治疗组小鼠MCU的表达较模型组明显减少(P<0.05)。结论 输注miR-1可能通过调节MCU的表达来改善ISO诱导的小鼠心力衰竭。

Abstract:

Objective To investigate the therapeutic effect of intravenous administration of a microRNA-1 (miR-1) agomir on isoproterenol (ISO)-induced heart failure (HF) in mice. MethodsMouse models of HF were established by intraperitoneal injection of ISO for 28 consecutive days at a daily dose of 60 mg/kg, and the control mice were injected with normal saline in the same manner. The success of modeling was verified by echocardiography on the next day after completion of the injections. On days 1 and 4 after successful modeling, the mice were received injections of a miR-1 agomir (miR-1 group) or a control agomir (model group) via the tail vein; the control mice were injected with normal saline only. The 3 groups of mice were again subjected to echocardiography on day 7. At the end of the experiment, the mice were sacrificed for assessing ventricular remodeling using HE staining, Sirius Red staining, WGA staining and Ki67 assay; the levels of serum NT-proBNP were detected using enzyme-linked immunosorbent assay, and the expression of mitochondrial calcium uniporter (MCU, the target gene of miR-1) in the cardiac tissues was detected with Western blotting and immunohistochemical staining. ResultsThe HF model was successfully established by intraperitoneal injections of ISO for 28 consecutive days. Intravenous administration of the miR-1 agomir significantly improved cardiac function and ventricular remodeling. Compared with that in the model group, the serum level of NT-proBNP in the HF models was significantly lowered following treatment with the miR-1 agomir, but still remained higher than that in the control group (P<0.05). The results of Western blotting and immunohistochemistry demonstrated a significant reduction of the expression of MCU in the cardiac tissues of miR-1-treated mice (P<0.05). ConclusionIntravenous injection of the miR-1 agomir can improve ISO-induced HF in mice probably by modulating MCU expression in the cardiac tissues.

参考文献/References:

[1]JOHNSON F L. Pathophysiology and etiology of heart failure[J]. Cardiol Clin, 2014, 32(1): 9-19, vii. DOI: 10.1016/j.ccl.2013.09.015. 
[2]YANCY C W, JESSUP M, BOZKURT B, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the american college of cardiology foundation/american heart association task force on practice guidelines[J]. J Am Coll Cardiol, 2013, 62(16): e147-e239. DOI: 10.1016/j.jacc.2013.05.019. 
[3]LAM C S, TENG T K, TAY W T, et al. Regional and ethnic differences among patients with heart failure in Asia: the Asian sudden cardiac death in heart failure registry[J].Eur Heart J, 2016, 37(41): 3141-3153. DOI: 10.1093/eurheartj/ehw331. 
[4] WEIWEI C, RUNLIN G, LISHENG L, et al. Outline of the report on cardiovascular diseases in China, 2014 [J]. Eur Heart J Suppl, 2016, 18: F2-F11. DOI: 10.1093/eurheartj/suw030.
[5]ROSIK J, SZOSTAK B, MACHAJ F, et al. Potential targets of gene therapy in the treatment of heart failure[J]. Expert Opin Ther Targets, 2018, 22(9): 811-816. DOI: 10.1080/14728222.2018.1514012. 
[6]WAHLQUIST C, JEONG D, ROJAS-MUOZ A, et al. Inhibition of miR-25 improves cardiac contractility in the failingheart[J]. Nature, 2014, 508(7497): 531-535.DOI: 10.1038/nature13073.
[7]RINCON M Y, VANDENDRIESSCHE T, CHUAH M K. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation[J]. Cardiovasc Res, 2015, 108(1): 4-20. DOI: 10.1093/cvr/cvv205. 
[8]ZHU Z D, YE J Y, NIU H, et al. Effects of microRNA-292-5p on myocardial ischemia-reperfusion injury through the peroxisome proliferator-activated receptor-α/-γ signaling pathway[J]. Gene Ther, 2018, 25(3): 234-248. DOI: 10.1038/s41434-018-0014-y. 
[9]XU L J, WANG Q X, JIANG W, et al. MiR-34c ameliorates neuropathic pain by targeting NLRP3 in a mouse model of chronic constriction injury[J]. Neuroscience, 2019, 399: 125-134. DOI: 10.1016/j.neuroscience.2018.12.030. 
[10]NIE X, FAN J H, LI H P, et al. Mir-217 promotes cardiac hypertrophy and dysfunction by targeting PTEN[J]. Mol Ther Nucleic Acids, 2018, 12: 254-266. DOI: 10.1016/j.omtn.2018.05.013. 
[11]KALOZOUMI G, YACOUB M, SANOUDOU D. MicroRNAs in heart failure: Small molecules with major impact[J]. Glob Cardiol Sci Pract, 2014, 2014(2): 79-102.DOI: 10.5339/gcsp.2014.30.
[12]WU M F, WU D, WANG C G, et al.Hexabromocyclododecane exposure induces cardiac hypertrophy and arrhythmia by inhibiting miR-1 expression via up-regulation of the homeobox gene Nkx2.5[J]. J Hazard Mater, 2016, 302: 304-313. DOI: 10.1016/j.jhazmat.2015.10.004. 
[13]DINIZ G P, LINO C A, MORENO C R, et al. MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone[J]. J Cell Physiol, 2017, 232(12): 3360-3368. DOI: 10.1002/jcp.25781. 
[14]CURCIO A, TORELLA D, IACONETTI C, et al. MicroRNA-1 downregulation increases connexin 43 displacement and induces ventricular tachyarrhythmias in rodent hypertrophic hearts[J]. PLoS ONE, 2013, 8(7): e70158. DOI: 10.1371/journal.pone.0070158. 
[15]KARAKIKES I, CHAANINE A H, KANG S, et al. Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling[J]. J Am Heart Assoc, 2013, 2(2): e000078. DOI: 10.1161/JAHA.113.000078. DOI: 10.1161/JAHA.113.000078.
[16]罗水莲, 陈宇航, 石毓君, 等. microRNA-1抑制心肌特异性Dicer基因缺失小鼠心脏病理性重构[J]. 第三军医大学学报, 2017, 39(14): 1469-1475. DOI: 10.16016/j.1000-5404.201611030.
LUO S L, CHEN Y H, SHI Y J, et al. MicroRNA-1 prevents cardiac remodeling in mice with heart failure induced by Dicer ablation[J]. J Third Mil Med Univ, 2017, 39(14): 1469-1475. DOI: 10.16016/j.1000-5404. 201611030. 
[17]SZCZUREK W, SZYGUA-JURKIEWICZ B, SIEDLECKI , et al. Prognostic scales in advanced heart failure[J]. Kardiochir Torakochirurgia Pol, 2018, 15(3): 183-187. DOI: 10.5114/kitp.2018.78444.
[18]COWGER J A, RADJEF R. Advanced heart failure therapies and cardiorenal syndrome[J]. Adv Chronic Kidney Dis, 2018, 25(5): 443-453. DOI: 10.1053/j.ackd.2018.08.012. 
[19]JAYAWARDENA T M, EGEMNAZAROV B, FINCH E A, et al. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes[J]. Circ Res, 2012, 110(11): 1465-1473. DOI: 10.1161/CIRCRESAHA.112.269035. 
[20]ZAGLIA T, CERIOTTI P, CAMPO A, et al. Content of mitochondrial calcium uniporter (MCU) in cardiomyocytes is regulated by microRNA-1 in physiologic and pathologic hypertrophy[J]. Proc Natl Acad Sci USA, 2017, 114(43): E9006-E9015. DOI: 10.1073/pnas. 1708772114. 
[21]KIM J C, SON M J, WOO S H. Regulation of cardiac calcium by mechanotransduction: Role of mitochondria[J]. Arch Biochem Biophys, 2018, 659: 33-41. DOI: 10.1016/j.abb.2018.09.026. 
[22]YU Z Q, CHEN R Z, LI M H, et al. Mitochondrial calciumuniporter inhibition provides cardioprotection in pressure overload-induced heart failure through autophagy enhancement[J]. Int J Cardiol, 2018, 271: 161-168. DOI: 10.1016/j.ijcard.2018.05.054.
[23]TOMAR D, DONG Z W, SHANMUGHAPRIYA S, et al. MCUR1 is a scaffold factor for the MCU complex function and promotes mitochondrial bioenergetics[J]. Cell Rep, 2016, 15(8): 1673-1685. DOI: 10.1016/j.celrep.2016.04.050.
 

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更新日期/Last Update: 2019-07-22