Faculty Collaboration Database

Combining patient proteomics and in vitro cardiomyocyte phenotype testing to identify potential mediators of heart failure with preserved ejection fraction. J Transl Med 2016 Jan 20;14:18

Date

01/23/2016

Pubmed ID

26792056

Pubmed Central ID

PMC4719542

DOI

10.1186/s12967-016-0774-3

Scopus ID

2-s2.0-84955276098 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

BACKGROUND: 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.

METHODS AND RESULTS: 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.

CONCLUSIONS: 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. 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.

Author List

Raphael R, Purushotham D, Gastonguay C, Chesnik MA, Kwok WM, Wu HE, Shah SJ, Mirza SP, Strande JL

Author

Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Amino Acid Sequence
Calgranulin A
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Female
Heart Failure
Humans
Induced Pluripotent Stem Cells
Male
Middle Aged
Molecular Sequence Data
Myocytes, Cardiac
Peptides
Phenotype
Proteome
Proteomics
Recombinant Proteins
Reproducibility of Results
Stroke Volume
Tandem Mass Spectrometry
Ultrasonography