Since the demonstration nearly 20 years ago that mutations of bone morphogenic protein receptor 2 (BMPR2) are associated with heritable pulmonary arterial hypertension [1–4], investigators have postulated that altered BMPR2 signalling, whether inherited or acquired, may be a novel therapeutic target for pulmonary arterial hypertension (PAH) of all aetiologies. Enhancing BMPR2 activity in animal models of pulmonary hypertension attenuates the severity of pulmonary vascular growth and proliferation [5, 6], although these models have not been predictive of responses in human disease. In the current issue of the European Respiratory Journal, Spiekerkoetter et al. [7] report that BMPR2 mRNA expression is attenuated in PAH and that FK506 (tacrolimus), a BMPR2 activator, produced no meaningful effects in a small, single-centre 16-week clinical trial in subjects with PAH due to a variety of aetiologies. While the authors identified several “FK506 responders” in a post hoc analysis, they found no difference in BMPR2 expression between “responders” and “non-responders”, nor did they observe any change in serologic biomarkers linked to increased BMPR2 signalling. BMPR signalling may be a therapeutic target for PAH, but further studies are needed http://ow.ly/KokP30efxbf

中文翻译：

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靶向骨形态发生蛋白受体 2 (BMPR2) 信号治疗肺动脉高压

自从近 20 年前证明骨形态发生蛋白受体 2 (BMPR2) 的突变与遗传性肺动脉高压有关 [1-4] 以来，研究人员假设改变的 BMPR2 信号传导，无论是遗传性还是获得性，都可能是一个新的治疗靶点适用于所有病因的肺动脉高压 (PAH)。在肺动脉高压动物模型中增强 BMPR2 活性会减弱肺血管生长和增殖的严重程度 [5, 6]，尽管这些模型并不能预测人类疾病的反应。在最新一期的《欧洲呼吸杂志》中，Spiekerkoetter 等人。[7] 报道 BMPR2 mRNA 表达在 PAH 中减弱，并且 FK506（他克莫司），一种 BMPR2 激活剂，在小范围内没有产生有意义的影响，单中心 16 周临床试验，针对多种病因导致的 PAH 受试者。虽然作者在事后分析中确定了几个“FK506 反应者”，但他们发现“反应者”和“无反应者”之间 BMPR2 表达没有差异，他们也没有观察到与 BMPR2 信号传导增加相关的血清学生物标志物的任何变化。BMPR 信号可能是 PAH 的治疗靶点，但需要进一步研究 http://ow.ly/KokP30efxbf