IRX1 hypermethylation promotes heart failure by inhibiting CXCL14 expression

To identify the mechanism and functions of IRX1 in heart failure (HF) and provide evidence for new therapies. Bioinformatic analysis was performed to select target genes in HF cells compared to normal groups. Experimental rats were treated in a controllable manner to explore how IRX1 methylation accounted for this disease in vivo. Cardiac ultrasonic and morphologic examinations were conducted to test the mouse heart and evaluate the degree of cardiac impairment at in the level of organization. GSEA analysis revealed the relative enrichment of functions. Immunofluorescent assays, western blotting and qRT-PCR were used to determine the DNA methylation and expression levels. IRX1 was hypermethylated in heart failure and identified as a target gene by bioinformatic analysis. Transverse aortic constriction (TAC) induced heart failure in rats, while 5-aza-2MODIFIER LETTER PRIME-deoxycytidine (5-Aza) alleviated heart failure in rats according to medical cardiac indexes. Western blotting and qRT-PCR revealed that a conspicuous difference in the expression of IRX1 and CXCL14 between HF and normal cardiac cells. As a result of gene methylation, left ventricular hypertrophy and cardiac fibrosis is usually accompanied by heart failure. Moreover, is the results implied that the demethylation of IRX1 improves heart failure in vivo and in vitro. IRX1 methylation induced damaged cardiac function and even heart failure, which has important implications for HF treatment and diagnosis.