Combining patient proteomics and in vitro cardiomyocyte phenotype testing to identify potential mediators of heart failure with preserved ejection fraction

Journal of Translational Medicine
Roseanne RaphaelJennifer L Strande

Abstract

Heart 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. Proteomic 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. Platelets may harbor proteins associated with HFpEF...Continue Reading

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Citations

Sep 20, 2016·British Journal of Pharmacology·Luca SalaChristine L Mummery
Oct 11, 2016·Expert Review of Proteomics·Irene Izquierdo, Ángel García
Nov 23, 2017·European Journal of Heart Failure·Dimitrios FarmakisGerasimos Filippatos
Dec 30, 2016·Journal of Cardiovascular Translational Research·Alison J KriegelJennifer L Strande
Dec 21, 2016·Expert Review of Proteomics·Marika MokouHarald Mischak
Jun 12, 2019·Heart Failure Reviews·Michael SarheneFan Guanwei
Apr 28, 2020·European Heart Journal·Antoni Bayes-GenisJames L Januzzi
Dec 2, 2020·BMC Veterinary Research·Pinar LeventZeki Yilmaz
Jun 15, 2021·Cardiology Research and Practice·Kornela HałuchaIwona Bil-Lula

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Datasets Mentioned

BETA
A6BM72

Methods Mentioned

BETA
blood draw
ELISA

Software Mentioned

pClamp
SEQUEST
Visualize

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