Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways

Jude Taylor, Anna C.Y. Yeung, Anthony Ashton, Alen Faiz, Victor Guryev, Bernard Fang, Sean Lal, Mark Grosser, Cristobal G. dos Remedios, Filip Braet, Craig S. McLachlan, Amy Li

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number188
JournalJournal of Cardiovascular Development and Disease
Volume10
Issue number5
DOIs
Publication statusPublished - May 2023

Keywords

  • dilated cardiomyopathy
  • peripartum cardiomyopathy
  • RNAseq gene expression

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