| Title: |
Abstract 4365633: The 5,000+ Plasma Proteome of an Atherosclerosis Mouse Model Identifies Known and Potential Disease Drivers |
| Authors: |
Delwarde, Constance; Matamalas, Joan; Chelvanambi, Sarvesh; Kasai, Taku; Aikawa, Masanori; Singh, Sasha |
| Source: |
Circulation ; volume 152, issue Suppl_3 ; ISSN 0009-7322 1524-4539 |
| Publisher Information: |
Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: |
2025 |
| Description: |
Background: Mutations in the LDL receptor (LDLR) are causal for familial hypercholesterolemia, inciting the Ldlr-/- model for atherosclerosis. Despite >3,000 reports using this model, technical limitations have impeded efforts to identify candidate disease drivers in plasma. We capitalized on recent advances in mass spectrometry technologies to investigate whether dyslipidemia impacts plasma proteins implicated in human disease. Methods: Ldlr-/- mice were fed a chow or high-fat diet (HFD) for 3 (n= 27 per diet) or 6 months (n=12 per diet). Plasma samples were processed using a nanoparticle workflow (Seer), and peptides were analyzed using the Orbitrap TM Astral TM (Thermo) ( Fig.A ). Proteomes were queried against the Tabula Muris mouse single-cell and Gene Ontology (GO) databases; and queried against a GWAS list of 419 risk loci for coronary artery disease (CAD). Results: We sequenced 5,080 plasma proteins surpassing previous reports by 10-fold. The most intense proteins were the prototypical apolipoproteins whereas proteins associated with cytokine/chemokine signaling represent the previously unchartered mouse plasma proteome ( Fig.B) . To monitor sweeping changes over time, we divided the proteome into quartiles (Q1-Q4). Proteins with a sustained enrichment in HFD (n=705 remain within Q1) are indicative of liver cell subtypes (Tabula Muris, q |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1161/circ.152.suppl_3.4365633 |
| Availability: |
https://doi.org/10.1161/circ.152.suppl_3.4365633 |
| Accession Number: |
edsbas.A0F597BD |
| Database: |
BASE |