Abstract: Objective To explore the function and mechanism of circular RNA 0006104 (circ_0006104) in regulating proliferation, activation and extracellular matrix (ECM) synthesis of cardiac fibroblasts (CFs) induced by angiotensin Ⅱ (Ang Ⅱ). Methods The primary CFs of neonatal mice were isolated and divided into control group, circ_0006104 knockdown group, Ang Ⅱ group,Ang Ⅱ + circ_0006104 knockdown group and Ang Ⅱ + circ_0006104 knockdown+ miR-370-3p inhibitor.EDU immunofluorescence staining was used to detect the proliferation level of CFs; Western blot was used to detect activation related gene (α-SMA); RT-qPCR was used to detect the expression of collagen Ⅰ and Ⅲ (Col and Col Ⅲ). Results Circ_0006104 was screened by RNA-seq high-throughput sequencing results. In the primary CFs of neonatal mice, silencing circ_0006104 had no effect on the proliferation, activation and ECM synthesis of CFs under physiological conditions, while silencing circ_0006104 could significantly inhibit the proliferation, activation and ECM synthesis of CFs induced by Ang Ⅱ (P＜0.05). The molecules of circ_0006104 could bind to and negatively regulate miR-370-3p. The combined experimental results showed that inhibition of miR-370-3p significantly reversed the inhibitory effects of circ_0006104 silencing on the proliferation, activation and ECM synthesis of CFs induced by Ang Ⅱ (P＜0.05). Conclusions Knockdown of circ_0006104 inhibits Ang Ⅱ-induced CFs fibrosis by binding and negatively regulating miR-370-3p.

Key words: cardiac remodeling, cardiac fibroblasts, circ_0006104, miR-370-3p