AIMS One-third of DCM patients experience ventricular tachycardia (VT), but a clear biological basis for this has not been established. The purpose of this study was to identify transcriptome signatures and enriched pathways in the hearts of dilated cardiomyopathy (DCM) patients with VT. METHODS AND RESULTS We used RNA-sequencing in explanted heart tissue from 49 samples: 19 DCM patients with VT, 16 DCM patients without VT, and 14 non-failing controls. We compared each DCM cohort to the controls and identified the genes that were differentially expressed in DCM patients with VT but not without VT. Differentially expressed genes were evaluated using pathway analysis, and pathways of interest were investigated by qRT-PCR validation, Western blot, and microscopy. There were 590 genes differentially expressed in DCM patients with VT that are not differentially expressed in patients without VT. These genes were enriched for genes in the TGFß1 and TP53 signaling pathways. Increased fibrosis and activated TP53 signaling was demonstrated in heart tissue of DCM patients with VT. CONCLUSIONS Our study supports that distinct biological mechanisms distinguish ventricular arrhythmia in DCM patients.

中文翻译：

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扩张型心肌病室性心律失常的转录组特征揭示纤维化增加和 TP53 激活。


目的 三分之一的 DCM 患者会出现室性心动过速 (VT)，但尚未建立明确的生物学基础。本研究的目的是确定患有 VT 的扩张型心肌病 (DCM) 患者心脏中的转录组特征和丰富的通路。方法和结果 我们对 49 个样本的移植心脏组织进行了 RNA 测序：19 名患有 VT 的 DCM 患者、16 名不患有 VT 的 DCM 患者和 14 名未失败的对照组。我们将每个 DCM 队列与对照组进行比较，并确定了在患有 VT 而非无 VT 的 DCM 患者中差异表达的基因。使用通路分析评估差异表达基因，并通过 qRT-PCR 验证、蛋白质印迹和显微镜检查研究感兴趣的通路。有 VT 的 DCM 患者中有 590 个基因差异表达，而在无 VT 的患者中没有差异表达。这些基因富含 TGFβ1 和 TP53 信号通路中的基因。在伴有 VT 的扩张型心肌病患者的心脏组织中，纤维化增加并激活了 TP53 信号传导。结论 我们的研究支持不同的生物学机制区分 DCM 患者的室性心律失常。