Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression

Area of Science:

• Cardiovascular Biology
• Molecular Genetics
• Biomarker Discovery

Background:

• Heart failure (HF) is a global health crisis with significant morbidity and mortality.
• Understanding the molecular signatures of HF progression is crucial for developing effective treatments.
• Current knowledge of genetic factors influencing HF progression remains limited.

Purpose of the Study:

• To identify novel molecular biomarkers associated with heart failure progression.
• To investigate the role of specific genes in the development and advancement of HF.
• To validate potential biomarkers for predicting HF outcomes.

Main Methods:

• Generated multi-level transcriptomic data from left ventricular heart tissue of HF patients and healthy donors.
• Utilized Masson staining for fibrosis assessment and lasso regression to identify fibrosis-associated genes.
• Validated candidate genes using immunohistochemistry (IHC) and quantitative reverse transcription PCR (qRT-PCR).
• Measured plasma COL1A1 levels via ELISA in a validation cohort to predict HF progression.

Main Results:

• Differentially expressed genes (mRNAs, microRNAs, lncRNAs) were identified, potentially regulating extracellular matrix.
• COL1A1 was identified as a gene associated with fibrosis and HF progression, confirmed by IHC and qRT-PCR.
• Plasma COL1A1 levels ≥256.5 ng/ml predicted poor 1-year survival post-heart transplantation in HF patients (HR 7.4, 95% CI 3.5-15.8).

Conclusions:

• COL1A1 is a potential plasma biomarker for heart failure progression.
• Elevated COL1A1 levels are associated with adverse outcomes in HF patients awaiting transplantation.
• COL1A1 may aid in predicting short-term survival in patients with advanced heart failure.