Shared proteomic landscape between arteriosclerosis and cardiovascular endpoints: a Mendelian randomization and observational study integrating AlphaFold3 for structural prediction - PubMed
2 hours ago
- #Mendelian Randomization
- #Proteomics
- #Cardiovascular Disease
- Study integrated proteomics, Bayesian colocalization, Mendelian randomization, and structural modeling to explore shared plasma proteome between arteriosclerosis/atherosclerosis and CVD.
- Identified ten proteins potentially causally linked to arteriosclerotic/atherosclerotic markers and cardiovascular events; five increased and four decreased risk, with ABO showing mixed associations.
- Key proteins included ANGPTL4, APOB, BRAP, LPA, ZPR1 (risk-increasing) and DUSP13, FN1, IL6R, MMP12 (risk-reducing), mostly replicated in independent data.
- Mediation analysis indicated LPA's effect on stroke was largely mediated via carotid plaque (92.4%).
- AlphaFold3 structural modeling highlighted functional variants in proteins like ANGPTL4 and FN1, suggesting pathogenic mechanisms.
- Findings support shared proteomic signatures across vascular conditions, emphasizing vascular-bed-specific mechanisms for biomarker and therapeutic development.