Quantitative proteomics of changes in succinylated proteins expression profiling in left appendages tissue from valvular heart disease patients with atrial fibrillation

Background: Previous studies have suggested that proteomic modifications are closely associated with cardiovascular diseases. The aim of this study was to identify potential mechanisms by profiling the changes in succinylated protein expression in left appendage tissues from patients with valvular heart disease and atrial fibrillation (AF). Methods: Using dimethyl labeling for relative and absolute quantification-coupled high-performance liquid chromatography-tandem mass spectrometry, we analyzed the proteomics profiles and succinylation events in 18 left atrial appendage tissue samples from patients who underwent cardiac valvular surgery, including nine patients with permanent AF and nine patients with sinus rhythm (SR). Results: In total, after setting the quantification ratio > 1.3 and < 1:1.3 representing the up- and down-regulated cutoff values, respectively, 132 proteins were classified as targets of upregulation and 117 proteins as targets of downregulation. Within these proteins, 246 sites exhibited upregulated succinylation and 45 sites exhibited downregulated succinylation. Protein-protein interaction networks showed that the proteins exhibiting lysine succinylation and AF status were highly enriched in energy metabolism, extracellular matrix-related, and cellular structure-related proteins. These results were confirmed by western blot. Conclusions: The differences in succinylation level of energy metabolism-related proteins indicates the possible involvement of these proteins in AF of valvular heart disease patients, and provide insight for further analysis of their biological functions.