BackgroundHeart failure with ejection fraction (HFpEF) is a syndrome resulting from several co-morbidities in which specific mediators are unknown. The platelet proteome responds to disease processes. We hypothesize that the platelet proteome will change composition in patients with HFpEF and may uncover mediators of the syndrome.Methods and resultsProteomic changes were assessed in platelets from hospitalized subjects with symptoms of HFpEF (n = 9), the same subjects several weeks later without symptoms (n = 7) and control subjects (n = 8). Mass spectrometry identified 6102 proteins with five scans with peptide probabilities of ≥0.85. Of the 6102 proteins, 165 were present only in symptomatic subjects, 78 were only found in outpatient subjects and 157 proteins were unique to the control group. The S100A8 protein was identified consistently in HFpEF samples when compared with controls. We validated the fining that plasma S100A8 levels are increased in subjects with HFpEF (654 ± 391) compared to controls (352 ± 204) in an external cohort (p = 0.002). Recombinant S100A8 had direct effects on the electrophysiological and calcium handling profile in human induced pluripotent stem cell-derived cardiomyocytes.ConclusionsPlatelets may harbor proteins associated with HFpEF. S100A8 is present in the platelets of subjects with HFpEF and increased in the plasma of the same subjects. We further established a bedside-to-bench translational system that can be utilized as a secondary screen to ascertain whether the biomarkers may be an associated finding or causal to the disease process. S100A8 has been linked with other cardiovascular disease such as atherosclerosis and risk for myocardial infarction, stroke, or death. This is the first report on association of S100A8 with HFpEF.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0774-3) contains supplementary material, which is available to authorized users.

Introduction: The platelet proteome is an untapped resource for identifying novel proteins that may reflect a disease process. The platelet proteome is understudied in heart failure. We hypothesize that the platelet proteome will change composition in patients with heart failure with ejection fraction (HFpEF). Using mass-spectral analysis, we examined the platelet proteome from subjects with heart failure with preserved ejection fraction (HFpEF) to identify proteins associated with the disease process. Methods/Results: We conducted a case-controlled prospective study in which we drew blood samples from hospitalized subjects with symptoms of HFpEF (n=9), the same subjects several weeks later without symptoms (n=7) and control subjects (n=8). The subjects with HFpEF were older and had a higher incidence of atrial fibrillation and smoking compared to the control group. There were no significant differences in body mass index, and history of hypertension, hyperlipidemia, coronary artery disease or diabetes. The HFpEF group had increased LV wall thickness, left atrial volume, and diastolic dysfunction. Mass spectrometry of the platelet rich abstract obtained from the blood samples of the 3 groups identified 6,102 proteins with 5 scans with peptide probabilities of ≥0.85. Of the 6,102 proteins, 165 were present only in symptomatic subjects, 78 were only found in asymptomatic subjects and 157 proteins were unique to the control group. S100A8 and its receptor, CD36 were two proteins identified consistently in HFpEF samples when compared with controls. Using ELISA, we further confirmed that plasma S100A8 levels were increased in subjects with HFpEF (728±358) vs. control (314±154). Conclusion: Platelets may harbor proteins associated with HFpEF. S100A8 is present in the platelets of subjects with HFpEF and increased in the plasma of the same subjects. S100A8 has been linked with other cardiovascular disease such as atherosclerosis and risk for myocardial infarction, stroke, or death. This is the first report on the association between S100A8 and HFpEF.