MiR-19b and miR-16 cooperatively signaling target the regulator ADRA1A in Hypertensive heart disease.

BACKGROUND

Hypertensive heart disease (HHD) is one of the most important causes of disease-related deaths worldwide and brings great painful for patients. In recent years, increasingly evidences support the role of miRNAs in various physiology processes and human diseases. In the present study, we investigated whether ADRA1A regulated by miR-19b and miR-16 was involved in the pathogenic mechanism of HHD.

METHODS

HHD mice models were established with injection of Deoxycorticosterone acetate (Doca). Real-time PCR was used to detect miRNAs and ADRA1A expression. Western blot was used to detect ADRA1A expression. Cell apoptosis was determined by assaying caspase3/7 activation.

RESULTS

ADRA1A was the target gene of miR-19b and miR-16, the expression of miR-19b, miR-16 and ADRA1A were significantly increased in Doca-induced HHD cells. MiRNAs (miR-19b, miR-16) inhibitor significantly increased the expression of ADRA1A but decreased relative activity of caspase 3/7. MiRNA antagomir significantly increased the expression of ADRA1A and heart rate (HR), but significantly decreased systolic blood pressure (SBP), artery diastolic blood pressure (ADBP), fibrosis of ventriculus sinister and cell apoptosis of myocardial tissue that induced by Doca. However, the cooperation of miR-19b and miR-16 showed the better effect than either miR-19b or miR-16.

CONCLUSION

ADRA1A mediated by miR-19b and miR-16 played an important role in HHD, which functioned as a target gene for HHD therapy.