Anatomically resolved transcriptome and proteome landscapes reveal disease-relevant molecular signatures and systematic changes in heart function of end-stage dilated cardiomyopathy

Dilated cardiomyopathy (DCM), as characterized by the left ventricular dilatation and contractile dysfunction, is one of the molecular mechanisms of which are largely unexplored. Here, we profiled the region-resolved transcriptome and proteome of healthy and DCM human myocardial tissue and obtained the deep-coverage dataset consisting 7,605 proteins and 19,880 transcripts in four chambers of the human heart. On the basis of the core proteome and transcriptome characters of the healthy hearts, chamber-specific proteome alterations were further revealed in end-stage DCM, among which extracellular matrix (ECM), mitochondrial function, and muscle contraction were the most dysregulated biological processes. Protein-protein interaction network demonstrated divergent functional networks of DCM atrium and ventricle. Additionally, a 4-biomarker panel (CTSB, vWF, C9, and MFGE8) was established with promising diagnostic potential for the DCM. Collectively, our data provide a global proteomic basis of the chamber-specific cardiac tissue, and establish a protein catalog that holds promise for better definition and diagnosis of DCM.

Automated summary

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and contractile dysfunction, and its molecular mechanisms are not fully understood. This study examined the transcriptome and proteome of healthy and DCM myocardial tissue, identifying dysregulated processes such as extracellular matrix, mitochondrial function, and muscle contraction. Furthermore, a 4-biomarker panel (CTSB, vWF, C9, and MFGE8) was developed for the diagnosis of DCM.