肺动脉高压（PH）是肺动脉压进行性增高的高致死性疾病，肺动脉平滑肌细胞（PASMCs）增殖是其主要病理基础，但调控机制未明。我们发现在低氧诱导PASMCs中circ_0068481高表达，miR-361-3p低表达；circ_0068481能促进PASMCs增殖，且在PH患者外周血中高表达。生物信息学预测：circ_0068481可结合miR-361-3p调控5-羟色胺转运体(SERT)。SERT可促进5-羟色胺转运至PASMCs促进细胞增殖。由此我们推测：circ_0068481通过结合miR-361-3p靶向SERT促进PASMCs增殖和PH发生。本研究将建立低氧PH小鼠模型，结合临床组织样本，从细胞、动物、临床三个层次，阐明circ_0068481/miR-361-3p通过促进SERT导致PASMCs异常增殖的机制。本研究将进一步揭示PH的发病机制，为临床治疗PH提供新靶点。

Pulmonary hypertension (PH) is a disease with significant mortality characterized by increased pulmonary artery pressure. Pulmonary artery smooth muscle cells (PASMCs) proliferation plays a crucial role in the development of PH. The potential regulatory mechanism of PASMCs proliferation remains unclear. Our previous studies showed that in vitro, circ_0068481 expression was significantly upregulated, and miR-361-3p was down-regulated in abnormal proliferation PASMCs. circ_0068481 can promote PASMCs proliferation. Meanwhile,the serum circ_0068481 levels were elevated in PH patients. Bioinformatic analysis showed there were multiple miR-361-3p binding sites on the circ_0068481 nucleic acid sequence, and serotonin transporter (SERT) was a targeted gene of miR-361-3p. 5-hydroxytryptamine-induced proliferation of human PASMCs is known to be primarily mediated via SERT. Therefore, we hypothesize that circ_0068481 regulated PASMCs proliferation and promoted the development of PH by adsorbing miR-361-3p and upregulated SERT protein. We will validate this hypothesis in the following studies. We will further evaluate the regulatory effects of circ_0068481/miR-361-3p on downstream target proteins and PASMCs proliferation, and clarify the role of circ_0068481/miR-361-3p in PASMC proliferation and PH development in a hypoxia-induced mouse model, as well as in clinical PH patients. Our study will illustrate a novel regulatory mechanism for PH developing and provide therapeutic targets of PH.