The Function And Mechanism Of MiR-1 And MiR-199 In Cardiac Hypertrophy

Cardiac hypertrophy is a major factor that contributes to heart failure. It has been suggested that microRNAs are involved in hypertrophy. To investigate the roles of miR-1 and miR-199, the microRNAs abundantly expressed in cardiac tissue, in the pathogenesis of cardiac hypertrophy, a hypertrophic rat model of abdominal aortic constriction (AAC) and cultured cardiac myocytes were employed. The results showed that: 1) MiR-1 was found to be down-regulated in AAC 1 week heart tissue. The hypertrophy induced by phenylephrine (PE) in cultured neonatal myocytes was alleviated by transfecting with an adenoviral vector over-expressing miR-1. TWF-1, an actin-related protein, was predicted to be a potential target of miR-1 as indicated by bioinformatical analysis. Luciferase assay and Western blot confirmed that TWF-1 was inhibited by miR-1 under physiological conditions, as well as hypertrophic process. Myocytes transfected with TWF-1 over-expressing adenovirus showed hypertrophic characteristics including hypertrophic morphological changes and up-regulation of hypertrophic markers, suggesting that the protective effects of miR-1 against cardiac hypertrophy is generated at least partially through targeting TWF-1. 2) MiR-199 was significantly up-regulated in hypertrophic rat hearts. In cultured neonatal myocytes, miR-199 promoted the hypertrophic reaction and inhibited the expression of ANP. The bioinformatics predicts that SIRT1 and HIF1αmay be targeted by miR-199. These results suggest that miR-1 and miR-199 may play important roles in cardiac hypertrophy.