In Vivo and Ex Vivo Experimental Approach for Studying Functional Role of Notch in Pulmonary Vascular Disease.
In Vivo and Ex Vivo Experimental Approach for Studying Functional Role of Notch in Pulmonary Vascular Disease.
复制标题
研究Notch在肺血管疾病中功能作用的体内和离体实验方法。
DOI：
10.1007/978-1-0716-2201-8_17
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yuan,JasonX-J
中科院分区：
文献类型：
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作者：
Jain,PriteshP;Hosokawa,Susumu;Babicheva,Aleksandra;Zhao,Tengteng;Chen,Jiyuan;Thistlethwaite,PatriciaA;Makino,Ayako;Yuan,JasonX-J
肺动脉高压（PAH）是一种严重的疾病，其特征是持续的血管收缩、向心性壁增厚和血管重塑，导致肺血管阻力增加，导致右心衰竭和死亡。急性肺泡缺氧引起肺血管收缩，而持续缺氧引起肺动脉高压（PH）。Notch信号通路的激活参与了肺动脉平滑肌细胞（PASMCs）的PAH和慢性缺氧诱导的PH的形成，其部分作用是通过增强PASMCs内Ca 2+信号通路。药理学实验和遗传学方法使用实验性PH的动物模型（例如，慢性缺氧诱导的PH）已被常规用于研究PAH/PH的致病机制并确定新的治疗靶点。在这一章中，我们描述的协议，以调查Notch的作用，通过测量肺血流动力学在体内和肺动脉压离体在实验性PH小鼠模型。使用这些实验方案，可以研究Notch或Notch信号通路在肺血管疾病的致病机制中的作用，并通过靶向Notch配体和受体开发新的治疗方法。
Pulmonary arterial hypertension (PAH) is a severe disease characterized by sustained vasoconstriction, concentric wall thickening and vascular remodeling leading to increased pulmonary vascular resistance, causing right heart failure and death. Acute alveolar hypoxia causes pulmonary vasoconstriction, while sustained hypoxia causes pulmonary hypertension (PH). Activation of Notch signaling is implicated in the development of PAH and chronic hypoxia induced PH via partially its enhancing effect on Ca2+signaling in pulmonary arterial smooth muscle cells (PASMCs). Pharmacological experiments and genetic approach using animal models of experimental PH (e.g., chronic hypoxia-induced PH) have been routinely utilized to study pathogenic mechanisms of PAH/PH and identify novel therapeutic targets. In this chapter, we describe protocols to investigate the role of Notch by measuring pulmonary hemodynamics in vivo and pulmonary arterial pressure ex vivo in mouse models of experimental PH. Using these experimental protocols, one can study the role of Notch or Notch signaling pathway in the pathogenic mechanisms of pulmonary vascular disease and develop novel therapies by targeting Notch ligands and receptors.