Abstract 15735: Antibody-Based Plasma Proteomics Profiling Reveals New Markers of Cardiorespiratory Fitness

Background: Plasma proteins can be biomarkers of cardiovascular health status but also physiologic effectors that mediate health benefits. Cardiorespiratory fitness (CRF) is an integrative measure of cardiovascular and metabolic health and independent predictor of future cardiovascular disease (CVD) and mortality risk, however limited knowledge exists regarding its molecular transducers. We sought to expand upon prior proteomic studies of CRF using an antibody-based technology (Olink TM ). Hypothesis: Olink proteomic profiling will identify new markers and potential mediators of CRF. Methods: We measured plasma proteins (N=1,472) using Olink’s platform in a pilot study within the HERITAGE Family Study (N=209 participants, mean age=34 years, 56% female, 36% Black) before and after 20 weeks of endurance exercise training (ET). We performed multivariable linear regression to measure the association between protein levels and CRF measured by CPET (VO 2 max in ml*kg -1 *min -1 ) adjusting for age and sex. Lean body mass was measured by hydrostatic weighing. Protein changes after ET were assessed using paired Student’s t-tests. Results: We identified 70 proteins significantly associated (FDR q <0.05) with VO 2 max. Among these, 14 have not previously been measured in the context of CRF, including perilipin-1, a modulator of lipid homeostasis in adipocytes (beta=-3.8, q=2.4x10 -4 ); latent-transforming growth factor beta-binding protein 3 (beta=-2.6, q=1.3x10 -3 ), a key regulator of TGF-beta activation; and hydroxysteroid 11-beta dehydrogenase 1 (beta=3.2, q=1.2x10 -3 ), which regulates cortisol metabolism. Carbonic anhydrase (CA) XIV (CA14; beta=5.4, q=1.3x10 -8 ), a member of the CA family with extracellular activity, had the strongest positive association with VO 2 max in our primary model as well as after further adjusting VO 2 max for lean body mass. Further, CA14 levels increased significantly after ET (log2 fold change: 0.14, q=0.007). Conclusions: Antibody-based plasma proteomics profiling identified new markers of CRF, including a CA isoform that increases after ET. These findings motivate further study of CA14’s mechanistic role in CA14 and expanded proteomics profiling to investigate molecular transducers of CRF.