Mechanism of CREB1 in cardiac function of rats with heart failure via regulating the microRNA-376a-3p/TRAF6 axis.

Heart failure (HF) is a complicated disease resulting from impaired heart function. CREB1 is a candidate target in heart-concerning diseases. This paper attempts to explore the role of CREB1 in HF. Initially, the HF rat model was established by constricted abdominal aortic surgery and the cardiac function of HF rats was assessed by ultrasonic cardiogram. Levels of CK-MB and LDH and activity of Caspase-3 and Caspase-9 in HF rats were determined. Subsequently, myocardium pathological injury and myocardium apoptosis were detected. Additionally, the interactions between CREB1 and miR-376a-3p and between miR-376a-3p and TRAF6 were verified. The roles of CREB1, miR-376a-3p, and TRAF6 in HF were evaluated. In HF rats, CREB1 and miR-376a-3p were both downregulated while TRAF6 was upregulated. Besides, HF rats had decreased values of EF and FS, elevated levels of CK-MB and LDH, inflammatory infiltration, promoted cardiomyocyte apoptosis, and elevated activity of Caspase-3 and Caspase-9, which were all reversed by CREB1. Additionally, CREB1 activated miR-376a-3p expression, and miR-376a-3p targeted TRAF6 transcription. Both miR-376a-3p knockdown and TRAF6 overexpression annulled the protective role of CREB1 overexpression in cardiac function of HF rats. CREB1 activated miR-376a-3p expression to suppress TRAF6, thereby promoting the cardiac function of HF rats.