Nanoparticle-enabled plasma proteomics of a mouse atherosclerosis model

Area of Science:

• Proteomics
• Cardiovascular Disease Research
• Biomarker Discovery

Background:

• Dyslipidemia, characterized by high LDL-cholesterol, is a key risk factor for coronary heart disease.
• Ldlr-/- mice fed a high-fat diet (HFD) serve as a crucial model for studying atherosclerosis and metabolic disorders.

Purpose of the Study:

• To comprehensively profile plasma proteins in a well-established mouse model of experimental atherosclerosis.
• To identify low-abundant proteins previously undetected in this model.

Main Methods:

• Ldlr-/- mice were subjected to HFD for 3 or 6 months.
• Plasma samples were enriched using nanoparticle technology and analyzed via mass spectrometry (Orbitrap Astral).
• Tissue proteomics of aorta and liver were also performed for comparative analysis.

Main Results:

• Sequenced 5,080 plasma proteins, a tenfold increase over previous studies.
• Identified cytokine/chemokine signaling proteins as a previously uncharted component of mouse plasma proteome.
• Detected 120 coronary artery disease (CAD)-associated proteins from human GWAS in mouse plasma, with 4 showing altered abundance on HFD.

Conclusions:

• Nanoparticle-enhanced mass spectrometry enables novel plasma biomarker discovery in preclinical models.
• This approach facilitates monitoring of candidate proteins linked to human disease mechanisms.
• Opens new avenues for understanding atherosclerosis pathology and identifying understudied molecular contributors.