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

Abstract

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.

Post-myocardial infarction treatment with resiniferatoxin modulates the expression of important genes involved in inflammation, plaque stability and angiogenesis

“…Overexpression of THBS1 (thrombospondinin-1) was shown in literature to have deleterious cardiac effects and its expression was inhibited by RTX. A differential gene expression study 34 identified THBS-1 as a candidate biomarker for cardiac hypertrophy. Moreover, THBS-1 gene was overexpressed in endothelin-stimulated cardiomyocytes, leading to hypertrophy.…”

CCN proteins: opportunities for clinical studies—a personal perspective

“…Using data mining Johansson et al (2022) identified CCN2 as a putative biomarker of cardiac hypertrophy in an in vitro stem‐cell‐based cardiac hypertrophy model (ET1 utilizing treated human‐induced pluripotent stem‐cell‐derived CMs (hiPSC‐CMs)), compared with the gene expression of biopsies collected from hypertrophic human hearts. Again, analyzing the CCN2 interactome revealed CCN2 as a central node within many biological processes associated with cardiac function and the development of cardiac hypertrophy.…”