Journal article
Global plasma protein profiling reveals DCM characteristic protein signatures
Journal of proteomics, Vol.209, pp.103508-103508
10/30/2019
DOI: 10.1016/j.jprot.2019.103508
PMID: 31476444
Abstract
To identify potential biomarkers supporting better phenotyping and to improve understanding of the pathophysiology of dilated cardiomyopathy (DCM), this study comparatively analyzed plasma protein profiles of DCM patients and individuals with low normal and normal left ventricular ejection fraction (LVEF) by mass spectrometry.
After plasma depletion using a MARS Hu-6 column, global proteome profiling was performed using a LTQ-Orbitrap Velos mass spectrometer. To compare and confirm results, two different discovery sets of samples were investigated. Differentially abundant proteins are involved in lipid metabolism, coagulation, and acute phase response. Serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in a third independent patient cohort. Additionally, PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction.
The results highlight lipid metabolism and inflammation as the major pathways being altered in DCM patients in comparison to patients presenting with suspicious myocarditis to the hospital.
Several studies focused on the identification of heart failure (HF) associated protein signatures in blood plasma, but only few that are largely based on only small sample series considered specific HF pathologies. Therefore, we performed a comparative global blood plasma protein profiling of a larger sample of individuals with reduced left ventricular ejection fraction (LVEF) classified as dilated cardiomyopathy patients and individuals with normal LVEF but presenting with suspicious myocarditis. DCM patients displayed altered levels of proteins involved in lipid metabolism, coagulation, and acute phase response. The most reliable candidates, such as serum paraoxonase 1 (PON1), cystatin C, lysozyme C, apolipoprotein A-II, and apolipoprotein M were validated by targeted protein analysis in an independent patient cohort. PON1 levels were also determined by an ELISA. These data highlight PON1 as a potential marker for differentiating DCM patients not only from patients with normal LVEF, but also from heart failure patients with preserved ejection fraction.
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•Comparative plasma protein profiling of DCM patients and controls was performed.•Proteins of lipid metabolism, coagulation, and acute phase response are altered in DCM.•PON1, CytC, LysC, and ApoA-II are most reliable biomarker candidates.•Data highlight PON1 as potential marker to differentiate DCM and HFpEF patients.
Details
- Title: Subtitle
- Global plasma protein profiling reveals DCM characteristic protein signatures
- Creators
- Martin Andreas Feig - Universitätsmedizin GreifswaldCristina Pop - Universitätsmedizin GreifswaldGourav Bhardwaj - Universitätsmedizin GreifswaldPraveen Kumar Sappa - Universitätsmedizin GreifswaldMarcus Dörr - Universitätsmedizin GreifswaldSabine Ameling - Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, GermanyKerstin Weitmann - Universitätsmedizin GreifswaldMatthias Nauck - Universitätsmedizin GreifswaldKristin Lehnert - Universitätsmedizin GreifswaldDaniel Beug - Universitätsmedizin GreifswaldUwe Kühl - Charité - Universitätsmedizin BerlinHeinz-Peter Schultheiss - CS DiagnosticsUwe Völker - Universitätsmedizin GreifswaldStephan Burkhard Felix - Universitätsmedizin GreifswaldElke Hammer - Universitätsmedizin Greifswald
- Resource Type
- Journal article
- Publication Details
- Journal of proteomics, Vol.209, pp.103508-103508
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jprot.2019.103508
- PMID
- 31476444
- ISSN
- 1874-3919
- eISSN
- 1876-7737
- Grant note
- DOI: 10.13039/501100001659, name: German Research Foundation, award: SFB/TR 19; DOI: 10.13039/501100002347, name: Bundesministerium für Bildung und Forschung; DOI: 10.13039/100010447, name: German Centre for Cardiovascular Research, award: 81Z7400172; name: POSDRU, award: 107/1.5/S/78702; name: University of Medicine; name: Pharmacy “Iuliu Hatieganu”
- Language
- English
- Date published
- 10/30/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984359565802771
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