Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium

Objectives - Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM). Methods - We studied biopsies from 9 patients with stable chronic heart failure undergoing coronary artery bypass surgery (CABG) (EF 34%+/- 3%) and from 4 patients with ESFM undergoing heart transplantation (EF 17%+/- 5%). In CABG patients paired echocardiographic studies before and 6 months after revascularization classified dysfunctional myocardium as RDM or IRDM. Regions with preserved contractile function served as control. We used two-dimensional gel electrophoresis (2D-PAGE) and computerized image analysis to investigate myocardial protein expression. Proteins were identified by in-gel digestion and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results - Among 3 significantly altered protein spots in RDM we identified 2 up-regulated glycolytic enzymes. In IRDM 15 proteins were signficantly altered of which we identified 10, among these 6 were down-regulated mitochondrial enzymes. In ESFM 9 of 12 significantly altered protein spots were identified. Six were down-regulated mitochondrial enzymes. Conclusion - Myocardial metabolism may be involved in the progression of heart failure to irreversible dysfunction and end-stage heart failure.