Wang Ran-Ran, Yuan Tian-Yi, Wang Jian-Mei, Chen Yu-Cai, Zhao Jiu-Liang, Li Meng-Tao, Fang Lian-Hua, Du Guan-Hua
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030000, China.
Pharmacol Res. 2022 Jun;180:106238. doi: 10.1016/j.phrs.2022.106238. Epub 2022 Apr 30.
Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary dysfunctional disease, characterized by progressive vascular remodeling. Inflammation is an increasingly recognized feature of PAH, which is important for the initiation and maintenance of vascular remodeling. High levels of various inflammatory mediators have been documented in both PAH patients and experimental models of PAH. Similarly, multiple immune cells were found to accumulate in and around the wall of remodeled pulmonary vessels and in the vicinity of plexiform lesions, respectively. On the other hand, inflammation is also a bridge from autoimmune diseases to PAH. Autoimmune diseases always lead to chronic inflammation, characterized by the low-level persistent infiltration of immune cells, and elevated levels of several pro-inflammatory cytokines and chemokines. In addition, circulating autoantibodies are found in the peripheral blood of patients, indicating a possible role of autoimmunity in the pathogenesis of PAH. Thus, anti-inflammatory and immunotherapy might be new strategies to prevent or even reverse the process of PAH. Many anti-inflammatory agents and immunotherapies have been confirmed in animal models while some clinical trials employing immunotherapies are completed or currently underway. Here, we review pathological mechanisms associated with inflammation and immunity in the development of PAH, and discuss potential interventions for the treatment of PAH.
肺动脉高压（PAH）是一种严重的心肺功能障碍性疾病，其特征为进行性血管重塑。炎症是PAH日益被认识到的一个特征，对血管重塑的起始和维持至关重要。在PAH患者和PAH实验模型中均已记录到多种炎症介质水平升高。同样，分别发现多种免疫细胞在重塑的肺血管壁内和周围以及丛状病变附近积聚。另一方面，炎症也是自身免疫性疾病与PAH之间的桥梁。自身免疫性疾病总是导致慢性炎症，其特征为免疫细胞的低水平持续浸润以及几种促炎细胞因子和趋化因子水平升高。此外，在患者外周血中发现循环自身抗体，这表明自身免疫在PAH发病机制中可能起作用。因此，抗炎和免疫治疗可能是预防甚至逆转PAH进程的新策略。许多抗炎药物和免疫疗法已在动物模型中得到证实，同时一些采用免疫疗法的临床试验已经完成或正在进行中。在此，我们综述PAH发生发展过程中与炎症和免疫相关的病理机制，并讨论PAH治疗的潜在干预措施。
