Gender differences in electrophysiological gene expression in failing and non-failing human hearts.

Gender differences in electrophysiological gene expression in failing and non-failing human hearts.
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DOI:
10.1371/journal.pone.0054635
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Efimov IR
Efimov IR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ambrosi CM;Yamada KA;Nerbonne JM;Efimov IR

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越来越多的人类心脏组织可用于研究,这对于提高我们对性别、年龄和其他参数(如药物和心脏病)对心律失常易感性影响的理解至关重要。在这项研究中,我们的目的是比较89个离子通道亚基的mRNA表达,钙处理蛋白,和转录因子的心脏传导和心肌发生的重要性在左心房(LA)和心室(LV)的失败和非失败的人类心脏的两种性别。使用定制设计的Taqman基因阵列探测从衰竭的男性(n = 9)和女性(n = 7)以及从非衰竭的男性(n = 9)和女性(n =9)心脏制备的总RNA样品。       进行分析,以探讨性别,失败的状态,和腔表达之间的关系。分层聚类分析揭示了腔室特异性表达模式,但未能确定疾病或性别依赖性聚类。性别特异性分析显示,与男性LA相比,失败女性中编码Kv4.3、KChIP2、Kv1.5和Kir3.1的转录物的表达水平较低。然而,LV成绩单的分析并未显示基于性别的显著差异。总的来说,我们的数据强调了人类心脏中离子通道亚基的差异表达和转录重塑与性别和心脏疾病的关系。此外,这些数据集的可用性将允许开发疾病,性别,最重要的是,患者特异性心脏模型,能够利用mRNA表达等信息来预测心脏表型。
The increasing availability of human cardiac tissues for study are critically important in increasing our understanding of the impact of gender, age, and other parameters, such as medications and cardiac disease, on arrhythmia susceptibility. In this study, we aimed to compare the mRNA expression of 89 ion channel subunits, calcium handling proteins, and transcription factors important in cardiac conduction and arrhythmogenesis in the left atria (LA) and ventricles (LV) of failing and nonfailing human hearts of both genders. Total RNA samples, prepared from failing male (n = 9) and female (n = 7), and from nonfailing male (n = 9) and female (n = 9) hearts, were probed using custom-designed Taqman gene arrays. Analyses were performed to explore the relationships between gender, failure state, and chamber expression. Hierarchical cluster analysis revealed chamber specific expression patterns, but failed to identify disease- or gender-dependent clustering. Gender-specific analysis showed lower expression levels in transcripts encoding for Kv4.3, KChIP2, Kv1.5, and Kir3.1 in the failing female as compared with the male LA. Analysis of LV transcripts, however, did not reveal significant differences based on gender. Overall, our data highlight the differential expression and transcriptional remodeling of ion channel subunits in the human heart as a function of gender and cardiac disease. Furthermore, the availability of such data sets will allow for the development of disease-, gender-, and, most importantly, patient-specific cardiac models, with the ability to utilize such information as mRNA expression to predict cardiac phenotype.
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