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Plasma Proteomic Assessment of Calcific Aortic Valve Disease in Older Adults.
Tuesday,2025-04-08 14:54 America/Los_Angeles — ecterry
| Title | Plasma Proteomic Assessment of Calcific Aortic Valve Disease in Older Adults. |
| Publication Type | Journal Article |
| Year of Publication | 2025 |
| Authors | Bortnick, AE, Austin, TR, Hamerton, E, Gudmundsdottir, V, Emilsson, V, Jennings, LL, Gudnason, V, Owens, DS, Massera, D, Dufresne, L, Yang, T-Y, Engert, JC, Thanassoulis, G, Tracy, RP, Gerszten, RE, Psaty, BM, Kizer, JR |
| Journal | J Am Heart Assoc |
| Volume | 14 |
| Issue | 5 |
| Pagination | e036336 |
| Date Published | 2025 Mar 04 |
| ISSN | 2047-9980 |
| Keywords | Age Factors, Aged, Aged, 80 and over, Aortic Valve, Aortic Valve Stenosis, Biomarkers, Blood Proteins, Calcinosis, Chemokine CXCL12, Echocardiography, Female, Humans, Male, Mendelian Randomization Analysis, Proteomics, Severity of Illness Index |
| Abstract | <p><b>BACKGROUND: </b>Calcific aortic valve disease (CAVD), and ensuing severe aortic stenosis (AS), is the foremost valvular disorder of aging, yet preventive therapies are lacking. A better understanding of the molecular underpinnings of aortic valve calcification (AVC) is necessary to develop pharmacologic interventions.</p><p><b>METHODS AND RESULTS: </b>We undertook large-scale plasma proteomics in a cohort study of adults ≥65 years old, the CHS (Cardiovascular Health Study), to identify individual proteins associated with echocardiographic AVC and incident moderate/severe AS. Proteomics measurements were performed with the aptamer-based SomaLogic platform of ~5000 proteins. Significant proteins were validated in a second cohort, the AGES-RS (Age, Gene/Environment Susceptibility-Reykjavik Study), which assessed AVC and AS by computed tomography. The potential causal associations of replicated proteins were tested in 2-sample Mendelian randomization using identified cis protein quantitative trait loci in consortia having computed tomography-quantified AVC or AS as outcomes. Six proteins showed Bonferroni-corrected significant relationships with AVC in CHS. Three of these, CXCL-12 (C-X-C chemokine ligand 12), KLKB1 (kallikrein), and leptin, replicated in AGES-RS, of which the former 2 are novel. Only 1 protein, CXCL6, which showed a near-significant association with AS in the replication cohort, was significantly (positively) associated with incident AS. Mendelian randomization analysis was conducted for KLKB1, CXCL12, and CXCL6, which supported a causal relationship for higher KLKB1 with lower AVC (beta=-0.25, =0.009).</p><p><b>CONCLUSIONS: </b>This study of older adults newly identified and largely replicated associations of 3 circulating proteins with calcific aortic valve disease, of which the relationship of plasma KLKB1 may have a causal basis. Additional investigation is necessary to determine if KLKB1 could be harnessed for calcific aortic valve disease therapeutics.</p> |
| DOI | 10.1161/JAHA.124.036336 |
| Alternate Journal | J Am Heart Assoc |
| PubMed ID | 40008515 |
ePub date:
25/03