Transcriptome Analysis Identifies Proteostasis and Cell Survival Pathway Disruption in Peripartum Cardiomyopathy,...

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Peripartum cardiomyopathy (PPCM) is a rare but serious form of heart failure during late pregnancy or postpartum.
• The precise molecular mechanisms linking pregnancy stress to cardiomyocyte dysfunction in PPCM are not fully understood.

Purpose of the Study:

• To investigate the molecular pathways involved in PPCM using transcriptome-wide RNA sequencing.
• To identify key genes and signaling pathways contributing to PPCM pathogenesis.

Main Methods:

• RNA sequencing of left ventricles from PPCM patients and healthy controls.
• Differential gene expression analysis and Ingenuity Pathway Analysis (IPA).
• Upstream regulator and integrated network analyses.

Main Results:

• Identified 2891 differentially expressed genes in PPCM ventricles.
• Revealed activation of protein ubiquitination, EIF2 signaling, mitochondrial dysfunction, and apoptosis pathways.
• Highlighted suppression of CLPP and activation of COPS5 and TEAD1, indicating disrupted proteostasis and translational control.

Conclusions:

• PPCM is characterized by a collapse of proteostasis and impaired translational homeostasis.
• Findings suggest potential therapeutic targets in mitochondria, protein quality control, integrated stress response, and COP9 signaling pathways.