Objectives AF is usually initiated and maintained in the left atrium. There is convincing evidence demonstrating an important pathophysiological association between LA remodelling and atrial fibrillation. A recent microarray study of a pig model of AF demonstrated that the genomic changes are more pronounced in left than right atrium with considerable overlap in the genomic response. The objective of our study was to analyse the different expression profiles of energy metabolism related proteins between left and right atrial appendages from AF patients and provide a better understanding of the mechanisms in AF.
Methods We used iTRAQ-coupled 2-D LC-MS/MS technique to screen the expression profiles of the energy metabolism related proteins in left and right atrial appendages from patients in AF (n = 8). Specimens were pulverised and homogenised in a lysate buffer,then digested by trypsin and labelled with different iTRAQ tags. The pooled labelled peptides were analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Protein identification and relative iTRAQ quantification were performed with the ProteinPilot Software 4.0. Protein differentially expression were validated by Western blot analysis to verify the results obtained by iTRAQ proteomic studies.
Results Data from iTRAQ labelling and LC-MS/MS technique resulted in 1023 unique proteins from the cardiac tissues. Meanwhile, we identified 123 differential expressed proteins closely related to energy metabolism. Among those proteins, 39 of them are related to carbohydrate metabolism (5 proteins up-regulated and 11 down-regulated in left atrial appendage), 22 of them are involved in lipid metabolism (1 protein up-regulated and 4 down-regulated in left atrial appendage), 49 of them are related to biological oxidation (7 protein up-regulated and 24 down-regulated in left atrial appendage) and 13 others kinds of proteins (3 protein up-regulated in left atrial appendage, no protein down-regulated). Most of them are key enzymes participating in energy metabolic reactions. The down-regulated proteins have shown prominent advantages in quantity and significance in energy metabolism. Western blotting has further confirmed the content of cytochrome c oxidase subunit 5B between LAA and RAA from patients with mitral valve disease in permanent AF and also confirmed the reliability of the iTRAQ proteomic studies used in this study.
Conclusions In summary, though some proteins were up-regulated, most of the energy metabolic related proteins in the LAA of AF patients were down-regulated which demonstrated that the energy production status in atria myocardium during permanent AF was impaired. The decreased energy metabolism status of atrial may involved in the matrix of AF.