ArticleJournal of the American Heart Association2025
Protein Drug Targets for Abdominal Aortic Aneurysm and Proteomic Associations Between Modifiable Risk Factors and Abdominal Aortic Aneurysm.
Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Systolic blood pressure variability as a risk factor for abdominal aortic aneurysm: a prospective cohort study with genomic and proteomic profiling.European journal of epidemiology · 2026Article
- A sparse proteomic risk score incorporating plasma MMP12 level improves prediction of abdominal aortic aneurysm.medRxiv : the preprint server for health sciences · 2025Article
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Authors and funding
9 authors.
Funding
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Abstract
backgroundAbdominal aortic aneurysm (AAA) is a severe aortic disease for which no pharmacological interventions have yet been developed. This investigation focused on identifying protein-based therapeutic targets and assessing how proteins mediate the interplay between modifiable risk factors and AAA development.
methodsCausal inferences between plasma proteins and AAA were drawn using 2-sample Mendelian randomization, followed by comprehensive sensitivity testing, colocalization, and replication efforts. Further analyses included database interrogation, single-cell RNA data analysis, enrichment analysis, protein-protein interaction networks, and immunohistochemistry to map the tissue-specific expression of these proteins, their expression within AAA tissues, and their biological roles. Mediation Mendelian randomization was employed to evaluate the mediating effects of AAA-related proteins on the associations between AAA and 3 risk factors: hypertension, smoking, and obesity.
resultsA total of 43 proteins were identified as having causal links to AAA. Colocalization analysis pinpointed 13 proteins with strong evidence of colocalization with AAA. Of these, the causal involvement of 10 proteins was substantiated by external validation data. Consistent evidence for PCSK9 (proprotein convertase subtilisin/kexin type 9), IL6R (interleukin-6R), ECM1 (extracellular matrix protein 1), and ANGPTL4 (angiopoietin-related protein 4) was further validated through tissue immunohistochemistry and blood data. Moreover, Mendelian randomization analysis identified 10 proteins as mediators of the influence of hypertension, smoking, and obesity on AAA development.
conclusionsThis analysis identifies 4 proteins (PCSK9, IL6R, ECM1, and ANGPTL4) as high-priority therapeutic targets for AAA and emphasizes the intermediary role of plasma proteins in linking hypertension, smoking, obesity, and AAA. Further investigations are needed to clarify the specific roles of these proteins in AAA pathology.
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