Urinary peptides in heart failure: a link to molecular pathophysiology

Area of Science:

• Biochemistry
• Cardiology
• Proteomics

Background:

• Heart failure (HF) is a global health issue with complex pathophysiology.
• Current single biomarkers struggle to capture HF's diverse nature.
• Urinary peptides offer a potential avenue for understanding HF.

Purpose of the Study:

• To investigate associations between urinary peptides and different subtypes of heart failure (HF) including reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF) ejection fraction.
• To explore links between these peptide biomarkers and the molecular pathophysiology of HF.
• To identify potential novel biomarkers for HF diagnosis and management.

Main Methods:

• Analysis of urinary peptide profiles from 5608 participants in the Human Urinary Proteome database.
• Comparison of peptide profiles between HF subtypes (HFrEF, HFmrEF, HFpEF) and controls, matched for key clinical variables.
• Application of Mann-Whitney test with correction for multiple testing and unsupervised learning algorithms.
• Sequencing of significantly associated urinary peptides, with subsequent in silico analysis.

Main Results:

• 577 urinary peptides significantly associated with HF were identified, with 77% being collagen fragments.
• In silico analysis indicated that HF-associated urinary peptide changes reflect collagen turnover and immune response, linked to fibrosis.
• Unsupervised clustering successfully separated HF patients from controls (P < 0.0001) but did not distinguish between HF subtypes.

Conclusions:

• Heart failure, irrespective of ejection fraction, shows distinct urinary peptide profiles related to collagen turnover and inflammation.
• These urinary peptides hold promise as tools for early HF detection, prognostication, and predicting therapeutic response.
• Further research is warranted to validate these findings and explore clinical applications.