BACKGROUND

Cardiac hypertrophy may be classified as either physiological or pathological. Pathological hypertrophy has a complex etiology and is genetically regulated. In this study, we used a mouse model of cardiac hypertrophy to explore the mechanisms of gene regulation, in particular, modulation of the expression of target genes through transcription factor activity, regulation of immune and inflammation-associated genes and regulation of the alternative splicing of transcription factors.

METHODS

Mouse models of pathological cardiac hypertrophy were established by transverse aortic constriction (TAC). We overexpressed HSPA1A in mouse cardiac HL-1 cells. GO and KEGG pathway annotation database was used to analyze all DEGs.

RESULTS

The expression of differed significantly between TAC + dantrolene sham + dantrolene (Sham was the non-TAC group, and DMSO was the contrast agent), and TAC + DMSO sham + DMSO. The RNA-binding protein Zfp36 was found to be differentially expressed between both TAC + dantrolene sham + dantrolene and TAC + DMSO sham + DMSO. The expression of and was significantly different between TAC + dantrolene and TAC + DMSO. was found to selectively regulate the expression of non-coding RNAs related to cardiac hypertrophy, including Rn7sk and RMRP. The downregulated genes were mainly related to inflammation and the immune response. HSPA1A negatively regulated alternative splicing of and positively regulated alternative splicing of .

CONCLUSIONS

was closely related to cardiac hypertrophy. Zfp36 was also related to cardiac hypertrophy. Dantrolene may delay cardiac hypertrophy and ventricular remodeling by regulating the expression of the RNA-binding protein genes and . positively regulated the expression of the non-coding RNAs RN7SK and RMRP while negatively regulating the expression of inflammation- and immune response-related genes. can play a role in cardiac hypertrophy by regulating the alternative splicing of and .