Yang Liu, Wan Naifu, Gong Fanpeng, Wang Xianfeng, Feng Lei, Liu Guizhu
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Department of Vascular & Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Cell Dev Biol. 2023 Mar 17;11:1132060. doi: 10.3389/fcell.2023.1132060. eCollection 2023.
Pulmonary hypertension (PH) is a refractory and fatal disease characterized by excessive pulmonary arterial cell remodeling. Uncontrolled proliferation and hypertrophy of pulmonary arterial smooth muscle cells (PASMCs), dysfunction of pulmonary arterial endothelial cells (PAECs), and abnormal perivascular infiltration of immune cells result in pulmonary arterial remodeling, followed by increased pulmonary vascular resistance and pulmonary pressure. Although various drugs targeting nitric oxide, endothelin-1 and prostacyclin pathways have been used in clinical settings, the mortality of pulmonary hypertension remains high. Multiple molecular abnormalities have been implicated in pulmonary hypertension, changes in numerous transcription factors have been identified as key regulators in pulmonary hypertension, and a role for pulmonary vascular remodeling has been highlighted. This review consolidates evidence linking transcription factors and their molecular mechanisms, from pulmonary vascular intima PAECs, vascular media PASMCs, and pulmonary arterial adventitia fibroblasts to pulmonary inflammatory cells. These findings will improve the understanding of particularly interactions between transcription factor-mediated cellular signaling pathways and identify novel therapies for pulmonary hypertension.
肺动脉高压（PH）是一种难治性致命疾病，其特征为肺动脉细胞过度重塑。肺动脉平滑肌细胞（PASMCs）不受控制的增殖和肥大、肺动脉内皮细胞（PAECs）功能障碍以及免疫细胞的血管周围异常浸润导致肺动脉重塑，继而导致肺血管阻力和肺压力增加。尽管针对一氧化氮、内皮素-1和前列环素途径的各种药物已用于临床，但肺动脉高压的死亡率仍然很高。多种分子异常与肺动脉高压有关，众多转录因子的变化已被确定为肺动脉高压的关键调节因子，并且肺动脉血管重塑的作用也已得到强调。本综述整合了从肺血管内膜PAECs、血管中膜PASMCs、肺动脉外膜成纤维细胞到肺炎症细胞的转录因子及其分子机制之间的联系证据。这些发现将增进对转录因子介导的细胞信号通路之间相互作用的理解，并确定肺动脉高压的新疗法。
