The Jiangxi Key Laboratory of Molecular Medicine, Nanchang, China.
Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
J Cell Mol Med. 2020 Aug;24(16):9085-9096. doi: 10.1111/jcmm.15544. Epub 2020 Jul 8.
Heart failure (HF) is the end stage of most heart disease cases and can be initiated from multiple aetiologies. However, whether the molecular basis of HF has a commonality between different aetiologies has not been elucidated. To address this lack, we performed a three-tiered analysis by integrating transcriptional data and pathway information to explore the commonalities of HF from different aetiologies. First, through differential expression analysis, we obtained 111 genes that were frequently differentially expressed in HF from 11 different aetiologies. Several genes, such as NPPA and NPPB, are early and accurate biomarkers for HF. We also provided candidates for further experimental verification, such as SERPINA3 and STAT4. Then, using gene set enrichment analysis, we successfully identified 19 frequently dysregulated pathways. In particular, we found that pathways related to immune system signalling, the extracellular matrix and metabolism were critical in the development of HF. Finally, we successfully acquired 241 regulatory relationships between 64 transcriptional factors (TFs) and 17 frequently dysregulated pathways by integrating a regulatory network, and some of the identified TFs have already been proven to play important roles in HF. Taken together, the three-tiered analysis of HF provided a systems biology perspective on HF and emphasized the molecular commonality of HF from different aetiologies.
心力衰竭（HF）是大多数心脏病病例的终末期，可能由多种病因引发。然而，不同病因引发的心力衰竭是否具有分子基础的共性尚未阐明。为了解决这一问题，我们通过整合转录组数据和通路信息进行了三层分析，以探究不同病因引发的心力衰竭的共性。首先，通过差异表达分析，我们获得了 11 种不同病因引发的心力衰竭中经常发生差异表达的 111 个基因。其中一些基因，如 NPPA 和 NPPB，是心力衰竭的早期和准确生物标志物。我们还提供了一些候选基因供进一步实验验证，如 SERPINA3 和 STAT4。然后，我们通过基因集富集分析成功鉴定了 19 个经常失调的通路。特别是，我们发现与免疫系统信号、细胞外基质和代谢相关的通路在心力衰竭的发展中至关重要。最后，我们通过整合调控网络成功获得了 64 个转录因子（TFs）和 17 个经常失调的通路之间的 241 个调控关系，其中一些已鉴定的 TFs 已被证明在心力衰竭中发挥重要作用。综上所述，HF 的三层分析为 HF 提供了一个系统生物学视角，并强调了不同病因引发的 HF 的分子共性。
