The interplay between H19 and HIF-1 in mitochondrial dysfunction in myocardial infarction

Myocardial infarction(MI) causes prolonged ischemia of infarcted myocardial tissue, which triggers a wide range of hypoxia cellular responses in cardiomyocytes. Emerging evidence has indicated the critical roles of long non-coding RNAs(lncRNAs) in cardiovascular diseases, including MI. The purpose of this study was to investigate the roles of lncRNA H19 and H19/HIF-1 alpha pathway during MI. Results showed that cell injury and mitochondrial dysfunction were induced in hypoxia-treated H9c2 cells, accompanied by an increase in the expression of H19. H19 silencing remarkably diminishes cell injury, inhibits the dysfunctional degree of mitochondria, and de-creases the injury of MI rats. Bioinformatics analysis and dual-luciferase assays revealed that H19 was the hypoxia-responsive lncRNA, and HIF-1 alpha induced H19 transcription through direct binding to the H19 promoter. Moreover, H19 participates in the HIF-1 alpha pathway by stabilizing the HIF-1 alpha protein. These results indicated that H19 might be a potential biomarker and therapeutic target for myocardial infarction.