Abstract
To identify proteins involved in the molecular mechanisms of pressure overload-induced heart failure, we quantitatively analyzed the left ventricular proteomic profile in a transverse aortic constriction (TAC) mouse model, a well-established model of cardiac hypertrophy and dysfunction. Multidimensional LC-MS/MS in combination with Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labeling were used to analyze cardiac tissue samples and identify proteins that are differentially expressed in the left ventricle of mice that were challenged by TAC through 14 and 28 days. In this study, 1,748 high-quality reference proteins were identified compared with control mice, which showed 64 proteins up-regulated and 68 proteins down-regulated in the left ventricle of TAC mice through 14 days. Meanwhile, 46 proteins were upregulated and 40 proteins were down-regulated in the left ventricle of TAC mice through 28 days. Of all the differentially expressed proteins, we performed GO, pathway analysis and their interactions to the differentially expressed proteins and found that most of the proteins are related to cardiac muscle contraction, energy metabolism, occurrence of diseases and signal transduction. These proteins represent potential novel diagnostic and therapeutic targets for the treatment of pressure overload-induced heart failure.
Keywords: Cardiac remodeling, heart failure, iTRAQ, Multidimensional LC-MS/MS, proteomics, transverse aortic constriction (TAC).
Graphical Abstract