Pulmonary Section, Cliniques Universitaires de Mont-Godinne, University of Louvain, Yvoir, Belgium.
Semin Respir Crit Care Med. 2013 Oct;34(5):714-24. doi: 10.1055/s-0033-1356494. Epub 2013 Sep 13.
New treatments for pulmonary arterial hypertension (PAH) are a crucial need. The increased proliferation, migration, and survival of pulmonary vascular cells within the pulmonary artery wall in PAH have allowed successful transposition of pathophysiological elements from oncologic researches. Next steps will require translation of these biological advances in PAH therapeutic arsenal and guidelines. This review synthesizes recent data concerning the role of receptor tyrosine kinases and their inhibitors in PAH, with implications in animal models and humans. Results of clinical trials are now accumulating to establish beneficial role of tyrosine kinase inhibitors (TKIs) in PAH and further findings are expected in the near future. Beside this curative approach, evidences of a possible TKI-induced cardiotoxicity are emerging. These safety issues raise concern about a potential amplified harmful effect in PAH, a pathology characterized by an underlying cardiac dysfunction. In addition, analyses of PAH registries shed light on a selective pulmonary vascular toxicity triggered by TKIs, especially dasatinib. These possible dual effects of the TKIs in PAH need to be taken in account for future pharmacological development of this therapeutic class in PAH.
肺动脉高压（PAH）的新治疗方法是当务之急。PAH 中肺动脉壁内肺血管细胞的增殖、迁移和存活增加，使得从肿瘤研究中成功转移了病理生理因素。下一步将需要将这些生物学进展转化为 PAH 治疗武器库和指南。这篇综述综合了最近关于受体酪氨酸激酶及其抑制剂在 PAH 中的作用的数据，包括在动物模型和人类中的意义。目前正在积累临床试验结果，以确定酪氨酸激酶抑制剂（TKI）在 PAH 中的有益作用，预计在不久的将来会有进一步的发现。除了这种治疗方法外，TKI 诱导的心脏毒性的证据也在不断出现。这些安全性问题引起了人们对 PAH 中潜在放大的有害影响的关注，PAH 是一种以潜在的心脏功能障碍为特征的病理学。此外，PAH 登记处的分析揭示了 TKI 引发的选择性肺血管毒性，特别是达沙替尼。这些 TKI 在 PAH 中的可能双重作用需要在未来 PAH 治疗类药物的药理学开发中加以考虑。
