Decoding the Heart Failure Peptidome.

Area of Science:

• Cardiovascular Medicine
• Biochemistry
• Proteomics

Background:

• Heart failure (HF) diagnosis and treatment rely on peptides like angiotensin II and brain natriuretic peptide.
• Systematic, unbiased studies of the HF peptidome are currently lacking.
• Understanding the plasma peptidome could significantly improve HF patient care.

Purpose of the Study:

• To systematically explore the low molecular weight peptidome in patients with heart failure.
• To identify and rank peptides based on differential expression, bioactivity, and association with clinical outcomes.
• To uncover novel peptide biomarkers for improved HF diagnosis, prognostication, and treatment.

Main Methods:

• Cross-sectional mass spectrometry analysis of plasma from 486 HF patients and 98 controls.
• Quantification of 21,694 unique peptides.
• Peptide ranking based on upregulation in HF, pattern similarity to bioactive peptides (machine learning), and clinical outcome association.

Main Results:

• 1924 differentially expressed peptides identified between HF patients and controls.
• Key peptides identified include angiotensin-related peptides, GIP propeptides, osteocalcin, cholecystokinin, and peptides related to natriuretic peptide clearance receptor and integrin alpha-7.
• Hierarchical clustering revealed 3 HF patient clusters; one with lowest survival showed peptide patterns linked to acute phase response and inflammation.

Conclusions:

• This study uniquely identifies and ranks peptides by regulation and bioactivity in HF.
• Provides crucial peptide-level data complementing protein-based methods.
• Highlights peptides related to the renin-angiotensin system, natriuretic peptides, and cardiometabolic regulation as promising for HF research and clinical application.