Abstract
AimsThe disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery.MethodsWe used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system.ResultsWe identified 1262 differentially expressed genes (DEGs) and 269 proteins (DEPs) between DCM cases and healthy controls. Among the most significantly upregulated (>5-fold) proteins were GRK5, APOA2, IGHG3, ANXA6, HSP90AA1, and ATP5C1 (p< 0.01). On the other hand, the most significantly downregulated proteins were GSTM5, COX17, CAV1 and ANXA3. At least ten entities were concomitantly upregulated on the two analysis platforms: GOT1, ALDH4A1, PDHB, BDH1, SLC2A11, HSP90AA1, HSP90AB1, H2AFV, HSPA5 and NDUFV1. Gene ontology analyses of DEGs and DEPs revealed significant overlap with enrichment of genes/proteins related to metabolic process, biosynthetic process, cellular component organization, oxidative phosphorylation, alterations in glycolysis and ATP synthesis, Alzheimer’s disease, chemokine-mediated inflammation and cytokine signalling pathways.ConclusionThe concomitant use of transcriptome and proteome expression to evaluate global changes in DCM has led to the identification of sixteen commonly altered entities as well as novel genes, proteins and pathways whose cardiac functions have yet to be deciphered. This data should contribute towards better management of the disease.
Highlights
Until recently, endeavors to understand alterations in disease have been directed at independent analyses of the transcriptomic or proteomic changes
We used identical myocardial tissues from five dilated cardiomyopathy (DCM) hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the Applied Biosystems (ABI) high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system
We identified 1262 differentially expressed genes (DEGs) and 269 proteins (DEPs) between DCM cases and healthy controls
Summary
Endeavors to understand alterations in disease have been directed at independent analyses of the transcriptomic or proteomic changes. DCM is a manifestation of the thinning of one or both ventricle(s) from an unknown cause leading to impaired cardiac contractility and overt congestive heart failure or cardiac arrhythmias It presents an end product of myocardial damage triggered by a variety of factors such as toxic, metabolic or infectious agents, but may be triggered by mutations in genes encoding various cardiac-related proteins[5,6,7,8]. The consequence of these manifestations is heart failure associated with a gradual increase in left ventricular end-diastolic and end-systolic volumes, wall thinning and alteration in the shape of the chambers to a more spherical and less elongated form, termed left ventricular remodeling [9]. DCM is a product of interplay of changes in various interrelated signalling networks that in turn trigger multiple events in the progression to overt heart failure
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