Insight into the underlying molecular mechanism of dilated cardiomyopathy through integrative analysis of data mining, iTRAQ-PRM proteomics and bioinformatics

Abstract

Dilated cardiomyopathy (DCM) is a common cardiomyopathy worldwide, which is characterized by ventricular dilatation and systolic dysfunction. DCM is one of the most common diseases contributing to sudden death and heart failure. However, our understanding of its molecular mechanisms is limited because of its etiology and underlying mechanisms. Poor access to human myocardium is a significant limitation in the study of DCM. Firstly, DCM disease target genes were downloaded from public databases, and 935 genes were identified as key target genes. Next, a total of 787 differentially expressed proteins (DEPs), including 353 up-regulated and 434 down-regulated proteins, were identified in our animal experiment. The functional annotation of these DEPs revealed complicated molecular mechanisms including oxidation-reduction process, tricarboxylic acid cycle, protein folding, and triggered a series of molecular pathways involving TCA cycle, Oxidative phosphorylation, Cardiac muscle contraction. Finally, the DEPs were analyzed for association with the target genes screened in the public dataset. The overlapping proteins were validated by parallel reaction monitoring (PRM). We obtained 154 key proteins and further determined the importance of these three pathways. Together, this study provided deep insights into the detailed molecular mechanisms of DCM and facilitated the identification of potential proteins associated with it.