Abstract: Objective To explore the expression level of miR-499a-3p in the plasma of patients with heart failure (HF) and its potential mechanism. Methods The plasma from HF patients andhealthy controls was collected, and the expression level of miR-499a-3p was detected by RTqPCR. After transfecting miR-499a-3p mimics into human cardiomyoblast cells, CCK-8 was used to detect the effect of miR-499a-3p on cell proliferation. Flow cytometry and TUNEL were used to detect apoptosis, and Western blotting was used to detect the expression levels of apoptosis-related proteins. The heart failure cell model was established, and miR-499a-3p inhibitor was transfected, CCK-8 and flow cytometry were used to detect cell viability and apoptosis. Dual luciferase reporter gene assay was used to investigate the targeted binding of miR-499a-3p to GAB1. The effect of miR- 499a-3p on GAB1 expression were detected. Finally, miR-499a-3p mimics and GAB1 plasmid wereco-transfected into human cardiomyoblast cells to detect the functional changes. Results Compared with the healthy volunteers, the expression level of miR-499a-3p in the plasma of patients with HFwas significantly higher ( t = 77. 47, P < 0. 01). miR-499a-3p mimics significantly decreased theproliferation rate of human cardiomyoblast cells and increased the proportion of apoptotic cells andTUNEL-positive cells (P < 0. 05). After transfection of miR-499a-3p mimics, the expression levelof apoptosis-inhibiting protein Bcl-2 was decreased, while the expression levels of apoptosis-promoting proteins Caspase-3 and Bax were up-regulated. Further studies showed that miR-499a-3p was significantly overexpressed in heart failure cells, and after inhibiting the expression of miR-499a- 3p, the proliferation rate of heart failure cells was significantly increased, and the apoptosis ratiowas significantly decreased (P< 0. 05). miR-499a-3p could bind to the 3′-untranslated region (3′-UTR) of GAB1, and targetly inhibit GAB1 mRNA and protein expression. Moreover, overexpression of GAB1 reversed the effect of miR-499a-3p on proliferation and apoptosis of human cardiomyoblast cells. Conclusion miR-499a-3p is upregulated in patients with HF, which can affect the proliferation and apoptosis of human cardiomyoblast cells through targeted inhibition of GAB1 protein expression, thus participating in the progression of HF.

Key words: heart failure, miR-499a-3p, GAB1, cardiomyoblast, apoptosis