Up-regulation of miR-155 protects against chronic heart failure by inhibiting HIF-1

Background: Despite a crucial role of miR-155 in human cancers, its function in heart failure (HF) is still under investigation. This study was designed to explore its association with HF. Methods: The abdominal transverse aortic constriction (TAC) was adopted for establishment of mouse HF models. qRT-PCR and WB were adopted to detect the changes of miR-155, HIF-1 alpha, Cle-caspase-3, BCL2 and Bax levels in myocardial cells and heart tissues. The changes of cardiac function were checked by ultrasound. Additionally, luciferase reporter gene was adopted for interaction analysis of miR-155 with HIF-1 alpha, and in situ end labelling method was used for detecting myocardial apoptosis. Results: MiR-155 in myocardial tissue of HF mice was significantly down regulated. In HF mice injected with agomiR-155, the up-regulation of miR-155 strongly improved cardiac function, and also significantly lowered the protein levels of apoptosis-associated markers, C-caspase-3 and Bax, but up regulated Bcl-2. Additionally, HIF-1 alpha was identified as the direct target of miR-155. As expected, over-expression of HIF-1 alpha greatly reversed the effects of agomiR-155 on cardiac function and the expression of apoptosis-associated markers in heart tissues of HF mice. Conclusion: MiR-155 overexpression can suppress myocardial cell apoptosis through HIF-1 alpha, and strongly alleviate the cardiac function damage in HF mice, indicating the potential of miR-155/HIF-1 alpha axis to be a target for the diagnosis and therapy of HF.