In Vivo and Ex Vivo Experimental Approach for Studying Functional Role of Notch in Pulmonary Vascular Disease.

Abstract

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.

• Authors: Pritesh P Jain, Susumu Hosokawa, Aleksandra Babicheva, Tengteng Zhao, Jiyuan Chen, Patricia A Thistlethwaite, Ayako Makino, Jason X-J Yuan
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 2472 Pg. 209-220 ( 2022) ISSN: 1940-6029 [Electronic] United States
• PMID: 35674903 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Topics

• Animals
• Cell Proliferation
• Cells, Cultured
• Hypertension, Pulmonary
• Hypoxia (metabolism)
• Mice
• Muscle, Smooth, Vascular (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Pulmonary Artery
• Vascular Remodeling