Hsieh Meng-Chien Willie, Wang Wei-Ting, Yeh Jwu-Lai, Lin Chuang-Yu, Kuo Yur-Ren, Lee Su-Shin, Hou Ming-Feng, Wu Yi-Chia
Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
Department of Plastic Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan.
Biomedicines. 2022 Jun 15;10(6):1415. doi: 10.3390/biomedicines10061415.
Pulmonary arterial hypertension (PAH) is a rare yet serious progressive disorder that is currently incurable. This female-predominant disease unfolds as a pan-vasculopathy that affects all layers of the vessel wall. Five classes of pharmacological agents currently exist to target the three major cellular signaling pathways identified in PAH but are incapable of effectively reversing the disease progression. While several targets have been identified for therapy, none of the current PAH specific therapies are curative and cost-effective as they fail to reverse vascular remodeling and do not address the cancer-like features of PAH. Our purpose is to review the current literature on the therapeutic management of PAH, as well as the molecular targets under consideration for therapy so as to shed light on the potential role and future promise of novel strategies in treating this high-mortality disease. This review study summarizes and discusses the potential therapeutic targets to be employed against PAH. In addition to the three major conventional pathways already used in PAH therapy, targeting PDGF/PDGFR signaling, regulators in glycolytic metabolism, PI3K/AKT pathways, mitochondrial heat shock protein 90 (HSP90), high-mobility group box-1 (HMGB1), and bromodomain and extra-terminal (BET) proteins by using their specific inhibitors, or a pharmacological induction of the p53 expression, could be attractive strategies for treating PAH.
肺动脉高压（PAH）是一种罕见但严重的进行性疾病，目前无法治愈。这种以女性为主的疾病表现为一种影响血管壁各层的全血管病变。目前有五类药物可针对PAH中确定的三种主要细胞信号通路，但无法有效逆转疾病进展。虽然已经确定了几个治疗靶点，但目前没有一种PAH特异性疗法具有治愈性且具有成本效益，因为它们无法逆转血管重塑，也无法解决PAH的癌症样特征。我们的目的是回顾关于PAH治疗管理的当前文献，以及正在考虑用于治疗的分子靶点，以便阐明新策略在治疗这种高死亡率疾病中的潜在作用和未来前景。本综述研究总结并讨论了针对PAH可能采用的治疗靶点。除了PAH治疗中已经使用的三种主要传统途径外，通过使用其特异性抑制剂靶向血小板衍生生长因子/血小板衍生生长因子受体（PDGF/PDGFR）信号传导、糖酵解代谢调节剂、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）途径、线粒体热休克蛋白90（HSP90）、高迁移率族蛋白盒1（HMGB1）和溴结构域及额外末端（BET）蛋白，或通过药物诱导p53表达，可能是治疗PAH的有吸引力的策略。
