Proteome-wide protein concentrations in the human heart

Thin Thin Aye, Arjen Scholten, Nadia Taouatas, Andras Varro, Toon A.B. Van Veen, Marc A. Vos, Albert J.R. Heck

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52 Citations (Scopus)

Abstract

The largest component of the human heart, the left ventricle (LV), plays a major role in delivering blood throughout the body. Therefore, an in-depth detailed quantitative proteome analysis of the human LV is a valuable resource. For this purpose, a multifaceted proteomics approach combining differential sample fractionations (gel, strong cation exchange (SCX)), enzymatic digestions (trypsin, chymotrypsin, LysN), and peptide fragmentation techniques (CID and ETcaD) was used to enhance protein sequence coverage, identification confidence and quantitative abundance determination. Using stringent criteria, 3584 distinct proteins could be identified from the latest well-annotated Swissprot database (23000 entries). Commutatively, the over 130000 identified MS/MS spectra were used to assess concentrations of each identified LV protein through a combination of spectral counting methods. Among the most concentrated proteins, many currently used biomarkers for detection of myocardial infarction reside. These cardiac leakage markers have a good diagnostic power, but their prognostic potential seems limited. Discovery of markers that represent etiological determinants of cardiac disease require a shift of focus towards the signaling proteome. Therefore, a protein-class centered quantitative analysis of kinases, phosphatases and GTPases was adopted. These comparative analyses revealed many cardiac involved kinases (PKA, CaMKII, ERK) to reside among the most abundant signaling proteins, and also to mediate many observed in vivo phosphorylation sites. The abundance chart of signaling proteins may assist in identifying novel functional pathways, for instance through the abundant, but relatively little known, kinases STK38L and OXSR1. The obtained quantitative protein library of the human left ventricle is a valuable resource to isolate signaling based, putative biomarkers with concentrations likely to be detectable in plasma.

Original languageEnglish
Pages (from-to)1917-1927
Number of pages11
JournalMolecular BioSystems
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 1 2010

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

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    Aye, T. T., Scholten, A., Taouatas, N., Varro, A., Van Veen, T. A. B., Vos, M. A., & Heck, A. J. R. (2010). Proteome-wide protein concentrations in the human heart. Molecular BioSystems, 6(10), 1917-1927. https://doi.org/10.1039/c004495d