Fatty acid-binding proteins sustain endothelial glycolysis and arterial programming in pulmonary arterial hypertension

标题：脂肪酸结合蛋白维持内皮糖酵解和动脉编程 肺动脉高压 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。血管重塑和闭塞的潜在机制 血管病变的形成仍不清楚。脂肪酸代谢功能障碍与PAH相关。然而，在这方面， 脂肪酸代谢在调节肺血管重构中的机制作用 PAH的发病机制尚未报道。我们假设内皮脂肪酸结合蛋白 4和5（FABP 4 -5）通过HIF-2a/SOX 17调节内皮糖酵解和动脉编程 在PAH的发病机制中导致严重血管重塑的信号传导。我们将1）定义 使用多个转基因动物研究内皮FABP 4 -5在PAH发病机制中的新作用 模型2)阐明FABP 4 -5诱导动脉编程的细胞和分子机制 和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， 有效治疗患者的肺动脉高压。

Title: Fatty acid-binding proteins sustain endothelial glycolysis and arterial programming 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 vascular remodeling and obliterative vascular lesion formation remain unclear. Fatty acid metabolism dysfunction is linked to PAH. However, the mechanistic role of fatty acid metabolism in regulating pulmonary vascular remodeling in the pathogenesis of PAH has not been reported. We hypothesize that endothelial fatty acid-binding proteins 4 and 5 (FABP4-5) regulate endothelial glycolysis and arterial programming through HIF-2a/SOX17 signaling which contributes to severe vascular remodeling in the pathogenesis of PAH. We will 1) define the novel role of endothelial FABP4-5 in the pathogenesis of PAH using multiple transgenic animal models. 2) delineate the cellular and molecular mechanisms that FABP4-5 induces arterial programming and pathogenesis of PAH. Completing our proposed study will provide a novel therapeutic strategy for the effective treatment of PAH in patients.