Loss of BMPR-II promotes oxidative stress and inflammation in pulmonary arterial hypertension

BMPR-II 的缺失会促进肺动脉高压的氧化应激和炎症

• 批准号: G0802261/1
• 负责人: Elaine Soon
• 金额: $ 25.9万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802261%2F1
• 关键词: Loss; BMPR; II; promotes; oxidative

Pulmonary arterial hypertension is a devastating condition, typically affecting young women, which leads to death within three years of diagnosis without treatment. New treatments have improved symptoms but the overall outlook remains poor. The cause of this disease remained a mystery until the identification of genetic mutations in a receptor known as bone morphogenetic protein type II receptor, or BMPR-II. The identification of these mutations has provided the first real insight into the underlying cause of this condition. In Professor Morrell‘s laboratory we are trying to establish the connection between a mutation in BMPR-II and the narrowing of blood vessels in the lung, which characterise pulmonary arterial hypertension. A potentially important observation is that reduced function of the BMPR-II receptor makes cells more susceptible to inflammation. Since inflammation in blood vessels is known to contribute to pulmonary hypertension, this research may provide a novel link between the genetic defect and the progression of disease. If we can understand the mechanism by which BMPR-II mutation causes inflammation we may be able to block this process. It would then be possible to develop new treatments for this condition using, for example, anti-inflammatory approaches that are already under development for other diseases.

肺动脉高压是一种毁灭性的疾病，通常影响年轻女性，在诊断后三年内不经治疗就会导致死亡。新的治疗方法改善了症状，但总体前景仍然不佳。这种疾病的原因一直是个谜，直到在一种称为骨形态发生蛋白II型受体（BMPR-II）的受体中发现了基因突变。这些突变的鉴定为了解这种疾病的根本原因提供了第一个真实的见解。在莫雷尔教授的实验室里，我们正试图建立BMPR-II突变与肺血管狭窄之间的联系，后者导致肺动脉高压。一个潜在的重要观察结果是，BMPR-II受体功能的降低使细胞更容易受到炎症的影响。由于已知血管炎症会导致肺动脉高压，因此这项研究可能会提供遗传缺陷与疾病进展之间的新联系。如果我们能够理解BMPR-II突变导致炎症的机制，我们可能能够阻止这一过程。然后就有可能开发出针对这种疾病的新疗法，例如，使用已经在开发用于其他疾病的抗炎方法。