Changes in transcriptomic landscape in human end-stage heart failure with distinct etiology

Area of Science:

• Genomics
• Molecular Biology
• Cardiovascular Research

Background:

• Heart failure (HF) is a complex condition with diverse underlying causes.
• Noncoding RNAs (ncRNAs) are increasingly recognized for their regulatory roles in cardiovascular diseases.
• Understanding the molecular mechanisms across different HF etiologies is crucial for effective treatment.

Purpose of the Study:

• To investigate the role of noncoding RNAs (ncRNAs) in various types of heart failure (HF).
• To construct gene regulatory and co-expression networks for different HF etiologies.
• To identify common and distinct molecular pathways and potential biomarkers for HF.

Main Methods:

• RNA sequencing was performed on myocardial tissues from non-failing hearts and patients with restrictive cardiomyopathy (RCM), ischemic heart disease (IHD), and valvular heart disease (VHD).
• Differential expression analysis of mRNAs, lncRNAs, circRNAs, and miRNAs was conducted.
• Gene regulatory networks and gene co-expression networks were constructed to analyze molecular interactions.

Main Results:

• Complex regulatory networks involving lncRNAs, circRNAs, miRNAs, and mRNAs were identified in HF.
• Common molecular pathways were found across all HF types, alongside distinct pathways specific to RCM, IHD, and VHD.
• Novel HF biomarkers with potential for clinical application in HF staging and diagnosis were identified.

Conclusions:

• HF pathogenesis involves intricate regulatory networks of coding and noncoding RNAs.
• These networks exhibit both shared and etiology-specific molecular pathways.
• The identified biomarkers hold promise for improving clinical management and diagnosis of heart failure.