Heart failure (HF) is the end-stage of various diseases, especially ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). We aimed to investigate the common molecular mechanism of ICM and DCM. Differentially expressed genes (DEGs) of ICM or DCM samples compared with control were identified in GSE1869, GSE5406, GSE57338, GSE79962, GSE116250, and GSE46224 datasets. Functional enrichment analysis and protein–protein network analysis of the coregulated DEGs in at least four datasets were performed using the online tools of DAVID, the Metascape database, and the STRING database. Hub genes of HF were identified and validated by western blotting (WB) and immunohistochemistry in our tissue microarray (TMA). Seventy-four coregulated ICM and 126 coregulated DCM relevant DEGs were identified. Moreover, 59 common genes between ICM and DCM relevant DEGs were obtained, which were mainly involved in cardiac fibrosis and several signal pathways, such as Wnt signal pathway, PI3K-Akt signal pathway, and HIF-1A signal pathway. Among the six hub genes with top degrees, asporin (ASPN) had a relatively higher correlation with LVEF. Finally, TMA and WB results revealed that the ASPN protein was significantly increased in ICM and DCM left ventricular samples. The present study revealed some common molecular mechanisms of HF with different causes. Furthermore, ASPN may be a potential promising biomarker for HF.

Background: Rubinstein–Taybi syndrome (RTS) is a rare, congenital, plurimalformative, and neurodevelopmental disorder. Previous studies have reported that large deletions contribute to more severe RTS phenotypes than those caused by CREBBP point mutations, suggesting a concurrent pathogenetic role of flanking genes, typical of contiguous gene syndromes, but the detailed genetics are unclear.Results: This study presented a rare case of Rubinstein-Taybi (RT) syndrome with serious cardiac abnormalities. Based on the clinical and genetic analysis of the patient, theADCY9gene deletion was highlighted as a plausible explanation of cardiac abnormalities. Inadcy9morphant zebrafish, cardiac malformation was observed. Immunofluorescence study disclosed increased macrophage migration and cardiac apoptosis. RNA sequencing in zebrafish model highlighted the changes of a number of genes, including increased expression of the mmp9 gene which encodes a matrix metalloproteinase with the main function to degrade and remodel extracellular matrix.Conclusions: In this study, we identified a plausible new candidate geneADCY9of CHD through the clinical and genetic analysis of a rare case of Rubinstein-Taybi (RT) syndrome with serious cardiac abnormalities. By functional study of zebrafish, we demonstrated that deletion ofadcy9is the causation for the cardiac abnormalities. Cardiac apoptosis and increased expression of the MMP9 gene are involved in the pathogenesis.