Data Mining Identifies CCN2 and THBS1 as Biomarker Candidates for Cardiac Hypertrophy

Cardiac hypertrophy is a condition that may contribute to the development of heart failure. In this study, we compare the gene-expression patterns of our in vitro stem-cell-based cardiac hypertrophy model with the gene expression of biopsies collected from hypertrophic human hearts. Twenty-five differentially expressed genes (DEGs) from both groups were identified and the expression of selected corresponding secreted proteins were validated using ELISA and Western blot. Several biomarkers, including CCN2, THBS1, NPPA, and NPPB, were identified, which showed significant overexpressions in the hypertrophic samples in both the cardiac biopsies and in the endothelin-1-treated cells, both at gene and protein levels. The protein-interaction network analysis revealed CCN2 as a central node among the 25 overlapping DEGs, suggesting that this gene might play an important role in the development of cardiac hypertrophy. GO-enrichment analysis of the 25 DEGs revealed many biological processes associated with cardiac function and the development of cardiac hypertrophy. In conclusion, we identified important similarities between ET-1-stimulated human-stem-cell-derived cardiomyocytes and human hypertrophic cardiac tissue. Novel putative cardiac hypertrophy biomarkers were identified and validated on the protein level, lending support for further investigations to assess their potential for future clinical applications.

Automated summary

This study compares the gene expression patterns of an in vitro stem cell-based cardiac hypertrophy model with biopsies collected from hypertrophic human hearts. It identifies differentially expressed genes and corresponding secreted proteins, highlighting the role of CCN2 in cardiac hypertrophy. The study also reveals biological processes associated with cardiac function and the development of cardiac hypertrophy. These findings contribute to the identification of potential biomarkers for cardiac hypertrophy.