基于干细胞技术研究BMPRII信号缺陷引起肺动脉高压的机制

Pulmonary arterial hypertension (PAH) is a progressive disease with increased pulmonary vascular resistance and finally lead to the right heart failure. Pulmonary vascular remodeling and altered right heart function are two important pathological aspects of this disease. BMPR2 mutation has been identified in heritable PAH and congenital heart disease associated PAH. This project is aim to employ human pluripotent stem cell to study the effect of non-sense and missense mutation on the cardiopulmonary vascular cell differentiation and the potential mechanism. By generating novel double knockout PAH mouse model it is possible to clarify the developmental change caused by mutation. We would also derive the stem/progenitor cells from patients to examine the selectivity of the BMPRII signaling up-regulator on different classes of PAH, and develop new strategy for the personalized therapy of cadiopulmonary vascular disease.

肺动脉高压是一种肺血管阻力进行性升高，最终导致患者右心衰竭而死亡的肺血管病。肺动脉血管重构和右心功能改变是肺动脉高压病理的两个重要方面。 BMPR2突变存在于遗传性和先心病相关肺动脉高压，此次立项通过建立基于人多能干细胞的肺动脉高压模型，研究关键无意义突变和错义突变对心肺血管细胞分化的影响以及可能的分子作用机制；建立新型的肺动脉高压动物模型，从发育学角度研究致病机理，并进一步开展新型BMPRII信号上调剂的干预机制研究；通过建立患者来源干/祖细胞系，根据不同肺高压类型进行选择性药物干预实验， 为心肺血管疾病的个性化治疗提供新方案。

肺动脉高压是一种肺血管阻力进行性升高，最终导致患者右心衰竭而死亡的肺血管病。肺动脉血管重构和右心功能改变是肺动脉高压病理的两个重要方面。 BMPR2突变存在于遗传性和先心病相关肺动脉高压，此次立项通过建立基于人多能干细胞的肺动脉高压模型，研究关键错义突变对心肺血管细胞分化的影响以及右心衰竭失代偿的分子作用机制；建立新型的先心病相关肺动脉高压、结缔组织病相关肺动脉高压和肺静脉阻塞疾病动物模型，从发育学角度研究致病机理。通过建立对应的患者来源干/祖细胞系，进一步开展新型BMPRII信号上调剂的干预机制研究，为心肺血管疾病的治疗提供新方案。