Bcl-2 Is Involved in Cardiac Hypertrophy through PI3K-Akt Pathway

Abstract

Cardiac hypertrophy (CH) is a common cause of sudden cardiac death and heart failure, resulting in a significant medical burden. The present study is aimed at exploring potential CH-related pathways and the key downstream effectors. The gene expression profile of GSE129090 was obtained from the Gene Expression Omnibus database (GEO), and 1325 differentially expressed genes (DEGs) were identified, including 785 upregulated genes and 540 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway enrichment analysis of DEGs were then performed. Although there were no pathways enriched by downregulated genes, many CH-related pathways were identified by upregulated genes, including PI3K-Akt signaling pathway, extracellular matrix- (ECM-) receptor interaction, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy (HCM). In the deeper analysis of PI3K-Akt signaling pathway, we found all the signaling transduction pointed to B cell lymphoma-2- (Bcl-2-) mediated cell survival. We then demonstrated that PI3K-Akt signaling pathway was indeed activated in cardiac hypertrophy. Furthermore, no matter LY294002, an inhibitor of the PI3K/AKT signaling pathway, or Venetoclax, a selective Bcl-2 inhibitor, protected against cardiac hypertrophy. In conclusion, these data indicate that Bcl-2 is involved in cardiac hypertrophy as a key downstream effector of PI3K-Akt signaling pathway, suggesting a potential therapeutic target for the clinical management of cardiac hypertrophy.