Proteome-Wide Genetic Investigation of Large Artery Stiffness
The molecular mechanisms contributing to large artery stiffness (LAS) are not fully understood. The aim of this study was to investigate the association between circulating plasma proteins and LAS using complementary proteomic and genomic analyses. A total of 106 proteins associated with carotid-femoral pulse-wave velocity, a noninvasive measure of LAS, were identified in 1,178 individuals from the Asklepios study cohort. Mendelian randomization analyses revealed causal effects of 13 genetically predicted plasma proteins on pulse pressure, including cartilage intermediate layer protein-2, high-temperature requirement A serine peptidase-1, and neuronal growth factor-1. These findings suggest potential novel therapeutic targets to reduce LAS and its related diseases.
Authors
- Julio A. Chirinos (ORCID: https://orcid.org/0000-0001-9035-5670)
- Lei Zhao (ORCID: https://orcid.org/0000-0001-5027-2379)
- Ali Javaheri (ORCID: https://orcid.org/0000-0001-6657-331X)
- Oday Salman (ORCID: https://orcid.org/0000-0002-8390-1036)
- Marie‐Joe Dib (ORCID: https://orcid.org/0000-0001-7591-5684)
- Ernst R. Rietzschel (ORCID: https://orcid.org/0000-0002-8422-177X)
- Dietmar Seiffert (ORCID: https://orcid.org/0009-0006-4818-2407)
- Thomas P. Cappola (ORCID: https://orcid.org/0000-0002-9630-7204)
- Mark Richards (ORCID: https://orcid.org/0000-0002-2023-8177)
- Kushan Gunawardhana (ORCID: https://orcid.org/0000-0003-4236-1763)
- Payman L. Zamani (ORCID: https://orcid.org/0000-0002-9345-5834)
- David J. Gordon (ORCID: https://orcid.org/0000-0003-1830-4371)
- Bianca Pourmussa
- Dipender Gill (ORCID: https://orcid.org/0000-0001-7312-7078)
- Marc De Buyzere (ORCID: https://orcid.org/0000-0003-1277-1083)
- Jaclyn Dennis
- Laura Liu (ORCID: https://orcid.org/0000-0002-3171-3172)
- Tim De Meyer (ORCID: https://orcid.org/0000-0003-2994-9693)
- Douglas L. Mann (ORCID: https://orcid.org/0000-0002-2516-0145)
- Vanessa P. M. van Empel (ORCID: https://orcid.org/0000-0002-6864-0296)
- Christina Ebert (ORCID: https://orcid.org/0000-0003-0985-3547)
- Stephen Burgess (ORCID: https://orcid.org/0000-0001-5365-8760)
- Jordana B. Cohen (ORCID: https://orcid.org/0000-0003-4649-079X)
- Chang Ching-Pin
- Sushrima Gan (ORCID: https://orcid.org/0000-0002-0221-9925)
- Joe David Azzo
- Seavmeiyin Kun
Institutions
- National University of Singapore (SG)
- Washington University in St. Louis (US)
- University of Cambridge (GB)
- Hospital of the University of Pennsylvania (US)
- Ghent University Hospital (BE)
- Ghent University (BE)
- Maastricht University (NL)
- University of Bristol (GB)
- Bristol-Myers Squibb (United States) (US)
- SomaLogic (United States) (US)
- New Zealand Brain Research Institute (NZ)
- National University Heart Centre Singapore (SG)
- John Cochran VA Medical Center (US)
- Imperial College London (GB)
- University of Pennsylvania (US)
- University of Otago (NZ)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1016/j.jacbts.2024.05.017
- Citations
- 3
- Primary Topic
- Cardiovascular Health and Disease Prevention
- Type
- article
- Field-Weighted Citation Impact
- 1.21
Funders
- National Institutes of Health