TNFα等炎症因素在肺动脉高压内皮损伤中的调控机制

Pulmonary arterial hypertension is a disease with increased pulmonary vascular resistance, and finally leads to the right heart failure. It is characterized with inflammation involved vascular remodeling. The endothelial cell is the key initiating cell type in PAH. TNFα induces endothelial cell apoptosis, endothelial leak by interfering with BMP signaling. BMP type II receptor mutations occur in heritable and idiopathic pulmonary arterial hypertension， the deficiency of BMPRII induces the chemokines and adhesion factors, it also recruits inflammatory cells in pulmonary vascular lesion. This project will focus on the effects of genetic deficiency and the inflammation on vascular remodelling during PAH development. Thus the restoration of BMP signalling to regulate the inflammation and improve endothelial cells function offers therapeutic potential for both genetic and non-genetic forms of PAH.

肺动脉高压是一类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。它的典型病理特征是炎症参与的血管重构, 内皮细胞是启始这一过程的主要细胞类型。TNFα等炎症因子通过改变BMP信号启动内皮调亡、渗透。BMPII型受体突变存在于遗传性和特发性肺动脉高压患者，缺陷的BMP信号诱导内皮表达趋化因子和黏附分子，招募相关炎症细胞，成为血管重构发生过程中的重要组成部分。 本次申请项目将围绕着基因因素和炎症因素诱导的血管重构对肺动脉高压的发生机制进行探讨。并提出以BMP信号为靶点控制炎症进程、改善内皮功能的肺动脉高压治疗新方案。

肺动脉高压是一类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。根据世界卫生组织相关分类，结缔组织病相关的肺动脉高压属于第一类动脉性肺动脉高压，它的典型病理特征是免疫因素参与的血管重构, 内皮细胞是启始这一过程的主要细胞类型。LPS,TNFα等炎症因子通过炎症小体及改变BMP信号启动内皮焦亡、渗透。BMPII型受体自身抗体导致缺陷的BMPRII信号诱导内皮表达趋化因子和黏附分子，招募相关炎症细胞，成为血管重构发生过程中的重要组成部分。 本项目围绕着炎症因素和BMPRII信号通路的改变对肺动脉高压的发生机制进行探讨。并提出以BMP信号为靶点控制炎症进程、改善内皮功能的肺动脉高压治疗新方案。