University Hospital, Medical Clinic II/V, Giessen, Germany.
Adv Exp Med Biol. 2010;661:435-46. doi: 10.1007/978-1-60761-500-2_28.
Pulmonary Hypertension is a severe lung disease, which is characterized by vasoconstriction and remodelling of the vessel wall. Mostly addressing the increased vascular tone, prostacyclin and its analogues, endothelin-receptor antagonists and phosphodiesterase type 5 inhibitors have been approved for treatment of PAH and represent the current therapeutic options. Mechanistically, these vasodilators decrease pulmonary vascular resistance and reduce thereby shear stress, which is a strong proliferative stimulus per se. Beside the development of new vasodilators, current research focuses on the development of causal treatment regimens aiming a normalization of the vessel structure. Mechanistically, increased proliferation, migration and a resistance to apoptosis of vascular cells represent key events in disease progression. In this context, tyrosine kinase inhibitors like imatinib have been shown to possess reverse remodelling potential in preclinical models of pulmonary hypertension by inducing apoptosis and blocking proliferation. This book chapter describes the role of the platelet derived growth factor (PDGF) receptor and its antagonists for treatment of pulmonary hypertension.
肺动脉高压是一种严重的肺部疾病，其特征为血管收缩和血管壁重塑。目前已批准前列腺素及其类似物、内皮素受体拮抗剂和磷酸二酯酶 5 抑制剂用于治疗肺动脉高压，这些药物主要针对增加的血管张力，代表了目前的治疗选择。从机制上讲，这些血管扩张剂可降低肺血管阻力，从而减少剪切力，剪切力本身就是一种强烈的增殖刺激。除了开发新的血管扩张剂外，目前的研究还集中在开发针对病因的治疗方案，旨在使血管结构正常化。从机制上讲，血管细胞的增殖、迁移和抗凋亡能力的增加是疾病进展的关键事件。在这方面，酪氨酸激酶抑制剂如伊马替尼已被证明在肺动脉高压的临床前模型中具有逆转重构的潜力，通过诱导细胞凋亡和阻断增殖。本章描述了血小板衍生生长因子（PDGF）受体及其拮抗剂在肺动脉高压治疗中的作用。
