Background: Dilated cardiomyopathy (DCM) is an important cause of heart failure. Comprehensive data on blood plasma protein profiles associated with this disease are still rare. Therefore, we profiled samples of a DCM patient cohort to derive molecular markers that are related to specific cardiovascular phenotypes and mortality.
Methods: A retrospective analysis of a registry of 610 patients with non-familial DCM enrolled at the University Medicine Greifswald from 2004-2012 was performed. Quantitative protein intensities obtained by tandem mass spectrometry (MS) after depletion of six high abundant plasma proteins were used for the analysis of associations between circulating protein levels and phenotypes (e.g. body mass index (BMI), disease duration, mortality, left ventricular ejection fraction (LVEF) and left ventricle diameter at diastole corrected for body surface area (LVEDDI)).
Results: The analysis of plasma samples allowed the collection of quantitative data of 341 circulating proteins. The reproducibility of MS data acquisition was monitored using a quality control plasma pool displaying a MS analysis variance of 12% and total technical variance of 22%. Results for proteins being associated with age, sex, and BMI correlate with already published data and confirm the plausibility of the data obtained. In addition, linear regression analyses revealed only two proteins being associated with LVEDDI and a robust protein signature associated with systolic heart function (LVEF) as well as mortality. Results for associations with self-reported disease duration were less significant, probably due to the large range of values (0-30 months) and the unequal distribution among patients (90% with disease duration ≥6 months).
Conclusions: Proteomic profiling of plasma from a cardiovascular DCM patient cohort allowed generation of high quality protein data which are used for integrative analysis with other OMICS data and can be utilised for the identification of biomarkers for prediction of outcome in longitudinal studies.