Pulmonary arterial hypertension (PAH) is a rare disease associated with abnormally elevated pulmonary pressures and right heart failure resulting in high morbidity and mortality. Although the prognosis for patients with PAH has improved with the introduction of pulmonary vasodilators, disease progression remains a major problem. Given that available therapies are inadequate for preventing small-vessel loss and obstruction, there is active interest in identifying drugs capable of targeting angiogenesis and mechanisms involved in the regulation of cell growth and fibrosis. Among the mechanisms linked to PAH pathogenesis, preclinical studies have identified promising compounds that are currently being tested in clinical trials. These drugs target seven of the major mechanisms associated with PAH pathogenesis: bone morphogenetic protein signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. In this review, we discuss the preclinical studies that led to prioritization of these mechanisms, and discuss completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells, among others. We anticipate that the next generation of compounds will build on the success of the current standard of care and improve clinical outcomes and quality of life for patients with PAH.

肺动脉高压（PAH）是一种罕见疾病，与肺动脉压力异常升高和右心衰竭相关，导致高发病率和死亡率。尽管随着肺血管扩张剂的引入，PAH 患者的预后有所改善，但疾病进展仍然是一个主要问题。鉴于现有疗法不足以预防小血管丢失和阻塞，人们对识别能够靶向血管生成以及参与细胞生长和纤维化调节机制的药物产生了积极的兴趣。在与 PAH 发病机制相关的机制中，临床前研究已经确定了一些有前景的化合物，目前正在临床试验中进行测试。这些药物针对与 PAH 发病机制相关的七种主要机制：骨形态发生蛋白信号传导、酪氨酸激酶受体、雌激素代谢、细胞外基质、血管生成、表观遗传学和血清素代谢。在这篇综述中，我们讨论了导致这些机制优先化的临床前研究，并讨论了使用新型干预措施（例如 sotatercept、阿那曲唑、rodatristat ethy、酪氨酸激酶抑制剂和内皮祖细胞等）已完成和正在进行的 2/3 期试验。我们预计下一代化合物将建立在当前护理标准的成功基础上，并改善 PAH 患者的临床结果和生活质量。