General Capillary to Arterial Endothelial Cell Transition in Pulmonary Arterial Hypertension

肺动脉高压中毛细血管内皮细胞向动脉内皮细胞的转变

• 批准号: 10716738
• 负责人: Zhiyu Dai
• 金额: $ 72.17万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716738
• 关键词: Arteries; Blood Vessels; Blood capillaries; Capillary Endothelial Cell; Cessation of life; Data; Development; Disease; Endothelial Cells; Failure; Heart Hypertrophy; Human; Hypertension; Lesion; Lung; Pathogenesis; Patients; Progressive Disease; Pulmonary Vascular Resistance; Research; Rodent; SOX17 gene; Signal Transduction; effective therapy; mortality; novel therapeutic intervention; premature; programs; pulmonary arterial hypertension; pulmonary vascular remodeling; therapeutically effective; treatment strategy

Title: General Capillary to Arterial Endothelial Cell Transition in Pulmonary Arterial Hypertension Project Summary Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophy, failure, and premature death. The underlying mechanisms of loss of capillary endothelial cells (ECs) and obliterative vascular lesion formation remain unclear. Our preliminary data showed that arterial programing was evident in human PAH patients and rodents. We hypothesize that general capillary ECs program to arterial ECs through HIF-2-Cdk19/Sox17/Notch4 signaling which contributes to the pathogenesis of PAH. Completing our proposed study will provide a novel therapeutic strategy for the effective treatment of PAH in patients.

标题：肺动脉中的一般毛细血管至动脉内皮细胞转化 高血压 项目摘要 肺动脉高压（PAH）的特征是肺动脉压的进行性增加， 导致右心肥大的血管阻力和闭塞性肺血管重塑， 失败和过早死亡。毛细血管内皮细胞（ECs）损失的潜在机制， 闭塞性血管病变的形成仍不清楚。我们的初步数据显示 编程在人类PAH患者和啮齿动物中明显。我们假设一般的毛细血管内皮细胞 通过HIF-2 α-Cdk 19/Sox 17/Notch 4信号转导对动脉内皮细胞进行编程， PAH的发病机制。完成我们提出的研究将提供一种新的治疗策略， 有效治疗PAH患者。