Mediating role of proteomics in the association between per-and polyfluoroalkyl substance exposure and blood pressure in youth
By Jiawen Carmen Chen, Jesse A Goodrich, Jiawen Liao, Shiwen Li, Qiran Jia, Douglas I Walker, Elizabeth Costello, Tanya L Alderete, Michael I Goran, Damaskini Valvi, Shudi Pan, Brittney O Baumert, Vasilis Vasiliou, Sarah Rock, Sandrah P Eckel, Rob McConnell, Frank D Gilliland, Max T Aung, Zhanghua Chen, David V Conti, and Lida Chatzi
Environ Pollut.
December 15, 2025
DOI: 10.1016/j.envpol.2025.127336
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants linked to elevated blood pressure (BP). However, research has largely focused on adults and underlying mechanisms are not fully understood. We evaluated associations between PFAS and BP in youth and examine potential mechanisms by leveraging proteomics. We analyzed data from two cohorts at baseline and follow-up: 312 adolescents from Study of Latino Adolescents at Risk (SOLAR) (2001-2012) and 137 young adults from Children Health Study (CHS) (2014-2018). Baseline plasma PFAS were measured using liquid chromatography-mass spectrometry, with PFAS burden scores calculated. Baseline plasma proteins were measured using Olink's Cardiometabolic Panel I. Systolic and diastolic BP (SBP, DBP) were measured at baseline and follow-up, with standardized scores calculated for SOLAR. PFAS-BP associations were evaluated using linear regression, mixed-effects models, and Bayesian weighted quantile sum regression. Mediation analyses were used to assess proteins' mediation effect. Longitudinal analysis in SOLAR showed that one standard deviation (SD) higher in baseline PFCAs and total PFAS burden was associated with an average of 0.07 (95 % Confidence Interval [CI]: 0.01, 0.12) and 0.08 (95 % CI: 0, 0.17) higher DBP Z-score, respectively, while doubling PFOA and PFNA corresponded to 0.09 (95 % CI: 0, 0.19) and 0.15 (95 % CI: 0.04, 0.26) higher DBP Z-score, respectively. Longitudinal analysis in CHS showed that each SD higher in PFSAs and total PFAS burden was associated with an average of 1.45 mm Hg (95 % CI: 0.19, 2.71) and 1.46 mm Hg (95 % CI: 0.2, 2.71) higher DBP, respectively, while doubling PFOS, PFHxS, and PFHpS corresponded to 2.34 mm Hg (95 % CI: 0.4, 4.29), 1.19 mm Hg (95 % CI: 0.06, 2.32), and 2.69 mm Hg (95 % CI: 0.38, 4.99) higher DBP, respectively. Mediation analyses in both cohorts identified pro-inflammatory, pro-fibrotic galectin-3 as a common mediator, implicating inflammatory-fibrotic pathways in PFAS-BP link among youth.
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