Comparative Proteomic Analysis of Lipoprotein(a): Method-Dependent Profiles and Disease Pathways

Area of Science:

• Proteomics
• Biochemistry
• Cardiovascular Research

Background:

• Lipoprotein(a) [Lp(a)] is a key genetic risk factor for atherosclerotic cardiovascular disease (ASCVD).
• Lp(a)-associated proteins are implicated in inflammation, thrombosis, and vascular calcification.
• Methodological variability can affect the definition of the Lp(a) proteome.

Purpose of the Study:

• To define the high-confidence proteome of Lipoprotein(a) [Lp(a)].
• To investigate the impact of different proteomic analysis methods on Lp(a) composition.
• To identify pathways linking Lp(a) to ASCVD pathogenesis.

Main Methods:

• Immunoprecipitation of Lp(a) from human plasma using an apo(a)-specific antibody.
• Mass spectrometry analysis employing both in-gel digestion and automated in-solution proteolysis.
• Identification of high-confidence proteins detected by ≥3 unique peptides across both methods.

Main Results:

• In-solution proteolysis identified 92 proteins; in-gel digestion identified 55 proteins.
• A core proteome of 34 high-confidence proteins was consistently identified by both methods.
• These proteins are enriched in pathways for lipoprotein remodeling, coagulation, and extracellular matrix organization.

Conclusions:

• The proteome composition of Lp(a) is influenced by the analytical method used.
• A robust core proteome of 34 proteins provides biological insights into Lp(a)-mediated ASCVD.
• Understanding the Lp(a) proteome may elucidate mechanisms of cardiovascular risk.