Platelet Proteomics: A Glimpse Into Metabolic Dysfunction-Associated Steatotic Liver Disease Pathogenesis

Area of Science:

• Proteomics
• Liver Disease
• Platelet Biology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease with unclear mechanisms.
• Platelets are involved in inflammation, fibrosis, and vascular remodeling, extending beyond hemostasis.

Purpose of the Study:

• Investigate platelet proteomic alterations in MASLD.
• Explore the role of these alterations in disease progression.

Main Methods:

• Analyzed 25 MASLD patients and 21 viral-hepatitis controls.
• Isolated platelets from sinusoidal and peripheral blood.
• Utilized high-throughput mass spectrometry-based proteomics for protein profiling.

Main Results:

• Identified 1052 platelet proteins.
• Found decreased histidine-rich glycoprotein and ADP-ribosylation factor-like protein 8B in MASLD.
• Observed increased perforin-1 and macro-H2A1 in advanced MASLD, indicating immune activation and endothelial injury.
• Enriched docking protein 1 and TGF-β-induced protein IG-H3 in patients with fibrosis and venopathy.

Conclusions:

• Identified potential platelet-derived protein markers in MASLD related to immune regulation, vascular remodeling, and metabolic dysfunction.
• These findings require validation in a prospective, metabolically matched cohort to confirm disease specificity.