MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes.
MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes.
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DOI：
10.1371/journal.pntd.0003828
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发表时间：
2015
影响因子：
3.8
通讯作者：
Ferreira LR
中科院分区：
文献类型：
--
作者：
Navarro IC;Ferreira FM;Nakaya HI;Baron MA;Vilar-Pereira G;Pereira IR;Silva AM;Real JM;De Brito T;Chevillard C;Lannes-Vieira J;Kalil J;Cunha-Neto E;Ferreira LR
恰加斯病是由寄生虫克氏锥虫引起的，它开始于一个以高寄生虫血症为特征的短暂急性期，随后是一个几乎没有寄生虫的终生慢性期。心脏受累是最突出的表现，30%的感染者会出现心室复极异常，并伴有心肌炎、纤维化和心肌细胞肥大，机制不明。然而，对恰加斯病患者的后续研究以及对小鼠模型的研究表明，疾病急性期发生的临床症状和病理生理事件的强度与慢性期观察到的心脏病的严重程度相关。在本研究中，我们研究了 microRNA (miRNA) 在克氏锥虫感染引起的疾病进展中的作用，因为已知 miRNA 水平的变化与许多心血管疾病有关。我们在哥伦比亚 T.cruzi 菌株急性感染期间的小鼠心脏样本中筛选了 641 个啮齿动物 miRNA，并鉴定了多个在感染后显着改变的 miRNA。在感染后的所有三个分析时间点中，发现 17 个 miRNA 的调控显着失调。其中，6 个 miRNA 的表达与疾病相关的临床参数相关，例如寄生虫血症和最大心率校正 QT (QTc) 间期。计算分析发现，这六种 miRNA 的基因靶点涉及与心室除极和复极时间增加相关的网络和信号传导通路，而心室除极和复极时间是 QTc 间期延长的重要因素。这里提供的数据将指导进一步研究 microRNA 对恰加斯心脏病发病机制的贡献。恰加斯病是由原生动物寄生虫克氏锥虫引起的，影响着全世界 800 万人。终生感染始于短暂的急性期，这与血液中循环的寄生虫、组织寄生以及各种体征和症状（包括与心肌炎相关的体征和症状）有关。急性期结束后，约 30% 的慢性感染者会出现心室复极异常，伴有肥厚、心肌炎和纤维化，机制尚不清楚。 MicroRNA 在基因表达沉默中发挥着关键作用，是心血管系统生理学和病理生理学的重要组成部分。在这里，我们通过筛选心脏样本中的 641 个啮齿动物 miRNA，首次描述了急性克氏锥虫感染对宿主 miRNA 表达的影响。许多 miRNA 在感染后表达显着改变，其中一些与克氏锥虫寄生和心电图变化相关。通路分析结果表明，这些失调的 miRNA 可能会影响与心室除极和复极时间增加相关的基因网络和信号通路。我们的研究为 miRNA 对寄生虫学和心脏病结果相关基因的调控提供了新的见解。
Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms. Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase. In the present study we investigated the role of microRNAs (miRNAs) in the disease progression in response to T. cruzi infection, as alterations in miRNA levels are known to be associated with many cardiovascular disorders. We screened 641 rodent miRNAs in heart samples of mice during an acute infection with the Colombiana T.cruzi strain and identified multiple miRNAs significantly altered upon infection. Seventeen miRNAs were found significantly deregulated in all three analyzed time points post infection. Among these, six miRNAs had their expression correlated with clinical parameters relevant to the disease, such as parasitemia and maximal heart rate-corrected QT (QTc) interval. Computational analyses identified that the gene targets for these six miRNAs were involved in networks and signaling pathways related to increased ventricular depolarization and repolarization times, important factors for QTc interval prolongation. The data presented here will guide further studies about the contribution of microRNAs to Chagas heart disease pathogenesis. Chagas’ disease is caused by the protozoan parasite Trypanosoma cruzi and affects 8 million individuals worldwide. The life-long infection begins with a short acute phase, which is associated to parasites circulating in the bloodstream, tissue parasitism, and various signs and symptoms including those related to myocarditis. After resolution of the acute phase, about 30% of those chronically infected will develop abnormal ventricular repolarization with hypertrophy, myocarditis and fibrosis by yet undefined mechanisms. MicroRNAs play a key role in silencing gene expression and are essential elements of the physiology and pathophysiology of the cardiovascular system. Here we describe for the first time the effect of acute T. cruzi infection on host miRNA expression by screening 641 rodent miRNAs in heart samples. A number of miRNAs have significantly altered expression upon infection and several of them correlate with T. cruzi parasitism and electrocardiographic changes. Pathway analysis results suggest that these dysregulated miRNAs can potentially affect gene networks and signaling pathways related to increased ventricular depolarization and repolarization times. Our study provides new insights on miRNA regulation of genes relevant to parasitological and cardiological outcomes.
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影响因子：
7
作者：
Gibson, UEM;Heid, CA;Williams, PM
通讯作者：
Williams, PM
DOI：
10.1016/s0169-328x(99)00194-1
发表时间：
1999-08-25
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Itokawa, K;Sora, I;Uhl, GR
通讯作者：
Uhl, GR
影响因子：
20.1
作者：
Rao PK;Toyama Y;Chiang HR;Gupta S;Bauer M;Medvid R;Reinhardt F;Liao R;Krieger M;Jaenisch R;Lodish HF;Blelloch R
通讯作者：
Blelloch R
DOI：
10.1590/s0037-86822001000200001
发表时间：
2001-03-01
影响因子：
2
作者：
Camandaroba, Edson Luiz Paes;Campos, Rozalia Figueira;Andrade, Sonia G.
通讯作者：
Andrade, Sonia G.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y