Platelet-derived growth factor inhibition in idiopathic and familial pulmonary arterial hypertension

肺动脉高压是一种罕见但具有破坏性的疾病。它通常影响年轻女性，她们在运动时出现越来越多的呼吸困难，并在诊断后几年内导致死亡。目前的治疗方法可以在一定程度上改善症状，但大多数患者最终死于这种疾病。近年来，我们对肺动脉高压的遗传和分子基础的理解取得了进展，已经确定了这些患者肺血管中异常的一些关键生长因子通路。其中，血小板衍生生长因子（PDGF）途径有望成为新的治疗靶点。口服可用且耐受性良好的药物已经存在，针对其他疾病的这一途径。我们建议研究一种抑制PDGF通路的药物在重度肺动脉高压患者中的治疗潜力。此外，我们将对来自这些患者的细胞进行研究，以增加我们对这种药物如何治疗肺动脉高压的理解。

Pulmonary arterial hypertension is an unusual but devastating condition. It typically affects young women who present with increasing breathlessness on exertion and leads to death within a few years from diagnosis. Current therapies can give some improvement in symptoms but most patients eventually die of the disease. Recent advances in our understanding of the genetic and molecular basis of pulmonary arterial hypertension have identified some key growth factor pathways which are abnormal in the lung blood vessels of these patients. Amongst these, the platelet-derived growth factor (PDGF) pathway shows promise as a new target for treatment. Orally available and well tolerated drugs already exist which target this pathway in other diseases. We propose to study the therapeutic potential of a drug which inhibits the PDGF pathway in patients with severe pulmonary hypertension. In addition, we will undertake studies in cells derived from these patients to increase our understanding of how this drug works in pulmonary hypertension.