TY - JOUR
T1 - Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways
AU - Taylor, Jude
AU - Yeung, Anna C.Y.
AU - Ashton, Anthony
AU - Faiz, Alen
AU - Guryev, Victor
AU - Fang, Bernard
AU - Lal, Sean
AU - Grosser, Mark
AU - dos Remedios, Cristobal G.
AU - Braet, Filip
AU - McLachlan, Craig S.
AU - Li, Amy
N1 - Funding Information:
This research was partly supported by funding from Heart Research Australia (AWA; 2014-02) and the Bushell Foundation (AWA; [G180904, G151106]).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - dilated cardiomyopathy
KW - peripartum cardiomyopathy
KW - RNAseq gene expression
UR - http://www.scopus.com/inward/record.url?scp=85160276475&partnerID=8YFLogxK
U2 - 10.3390/jcdd10050188
DO - 10.3390/jcdd10050188
M3 - Article
AN - SCOPUS:85160276475
SN - 2308-3425
VL - 10
JO - Journal of Cardiovascular Development and Disease
JF - Journal of Cardiovascular Development and Disease
IS - 5
M1 - 188
ER -