Taylor Jude, Yeung Anna C Y, Ashton Anthony, Faiz Alen, Guryev Victor, Fang Bernard, Lal Sean, Grosser Mark, Dos Remedios Cristobal G, Braet Filip, McLachlan Craig S, Li Amy
Centre for Healthy Futures, Torrens University Australia, Surrey Hills, NSW 2010, Australia.
Respiratory Bioinformatics and Molecular Biology, School of Life Sciences, The University of Technology Sydney (UTS), Sydney, NSW 2007, Australia.
J Cardiovasc Dev Dis. 2023 Apr 23;10(5):188. doi: 10.3390/jcdd10050188.
Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors. Differential gene expression, enrichment analysis and cellular deconvolution were performed to identify key processes in disease pathology. PPCM and DCM display similar enrichment in metabolic pathways and extracellular matrix remodeling suggesting these are similar processes across end-stage systolic heart failure. Genes involved in golgi vesicles biogenesis and budding were enriched in PPCM left ventricles compared to healthy donors but were not found in DCM. Furthermore, changes in immune cell populations are evident in PPCM but to a lesser extent compared to DCM, where the latter is associated with pronounced pro-inflammatory and cytotoxic T cell activity. This study reveals several pathways that are common to end-stage heart failure but also identifies potential targets of disease that may be unique to PPCM and DCM.
围产期心肌病（PPCM）是一种罕见的急性发作性心力衰竭形式，发生在分娩前后原本健康的孕妇身上。虽然这些女性中的大多数对早期干预有反应，但约20%会进展为终末期心力衰竭，其症状类似于扩张型心肌病（DCM）。在本研究中，我们检查了来自终末期PPCM患者左心室的两个独立RNA测序数据集，并将基因表达谱与女性DCM患者和未患心力衰竭的供体进行了比较。进行了差异基因表达、富集分析和细胞反卷积，以确定疾病病理中的关键过程。PPCM和DCM在代谢途径和细胞外基质重塑方面表现出相似的富集，表明这些是终末期收缩性心力衰竭的相似过程。与健康供体相比，参与高尔基体囊泡生物发生和出芽的基因在PPCM左心室中富集，但在DCM中未发现。此外，免疫细胞群体的变化在PPCM中很明显，但与DCM相比程度较小，后者与明显的促炎和细胞毒性T细胞活性相关。这项研究揭示了终末期心力衰竭的几种常见途径，但也确定了可能是PPCM和DCM特有的疾病潜在靶点。
