Integrated analysis of the proteome and transcriptome in human ischemic cardiomyopathy

Abstract Background: Ischemic cardiomyopathy (ICM) is the primary cause of heart failure, which leads to an unacceptable rate of mortality and morbidity. The molecular mechanisms involved in ICM remains incompletely understood. This study aimed to investigate the molecular mechanisms of ICM by integrated proteome and transcriptome analyses.Methods and Results: Data independent acquisition (DIA) mass spectrometry and RNA-seq technologies were performed in left ventricular species from 5 ICM patients and 5 unused non-failing donors. A total of 546 differentially expressed proteins (DEPs) and 1080 mRNAs (DEGs) were identified in ICM compared with control, which were mainly involved in inflammatory/immune response, response to stress (such as hypoxia and reactive oxidative species), oxidative stress, and ECM (extracellular matrix) organization. Moreover, though the low correlation between transcriptome and proteome, 41 key genes were identified, which showed the same expression directions at mRNA and protein levels. Among them, HSP90AA1 occupied a central position in the PPI network. Furthermore, a differentially expressed lncRNA-mRNA-protein network was constructed, which consisted of 13, 11, and 11 differentially expressed lncRNAs, mRNAs, and proteins, respectively, and the expression of this network were validated by qRT-PCR.Conclusion: This identified some key genes and a lncRNA-mRNA-protein regulatory network involved in ICM, which should provide a framework for an in-depth interrogation into the complex molecular mechanisms of ICM.