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Published on: January 28, 2020
Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality
Toshiko Tanaka1, Sameera A Talegawkar2, Yichen Jin2
1Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA.
Insights
Cardiovascular health (CVH) is linked to longevity. This study identified 92 proteins associated with CVH, with 33 mediating the link between CVH and mortality, revealing underlying biological mechanisms.
Area of Science:
- Proteomics
- Cardiovascular Health
- Mortality Research
Background:
- Cardiovascular health (CVH) measures, incorporating behavioral and biological factors, demonstrate protective effects against all-cause mortality.
- The precise biological mechanisms linking CVH to mortality remain incompletely understood.
Purpose of the Study:
- To investigate the plasma proteomics profile associated with CVH.
- To determine if specific proteins mediate the relationship between CVH and all-cause mortality within the InCHIANTI study cohort.
Main Methods:
- Plasma samples from InCHIANTI study participants were analyzed for 1301 proteins.
- Statistical analyses identified proteins significantly associated with CVH and those mediating the CVH-all-cause mortality association.
Main Results:
- Ninety-two proteins were significantly associated with CVH (22 positive, 70 negative).
- Key proteins linked to CVH included leptin (LEP), fatty acid binding protein 3 (FABP3), Angiopoietin-2 (ANGPT2), and growth-differential factor 15 (GDF15).
- Thirty-three of these proteins significantly mediated the association between CVH and all-cause mortality, with mediation ranging from 5% to 30%.
Conclusions:
- Growth-differential factor 15 (GDF15) and insulin-like growth factor 2 (IGFBP2) were identified as significant mediators.
- Proteins linked to better CVH were enriched in pathways related to complement coagulation and GH/IGF suppression.
Abstract:
Measures of cardiovascular health (CVH) assessed by a combination of behavioral and biological factors has shown protective associations with all-cause mortality. The mechanisms underlying these associations have not been fully elucidated. In this study, we characterized the plasma proteomics profile of CVH and tested whether specific proteins mediated the associations between CVH and all-cause mortality in participants of the InCHIANTI study. Of the 1301 proteins tested, 92 proteins were associated with CVH (22 positively, 70 negatively). Proteins most strongly associated with CVH included leptin (LEP), fatty acid binding protein 3 (FABP3), Angiopoietin-2 (ANGPT2), and growth-differential factor 15 (GDF15). Of the 92 CVH-associated proteins, 33 proteins significantly mediated the associations between CVH and all-cause mortality, with percent mediation ranging from 5 to 30%. The most significant mediating proteins were GDF15 and insulin-like growth factor 2 (IGFBP2). Proteins associated with better CVH were enriched for proteins that reflect the suppression of the complement coagulation and GH/IGF pathways.
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