Pristane/Hypoxia (PriHx) Mouse as a Novel Model of Pulmonary Hypertension Reflecting Inflammation and Fibrosis

Circulation Journal : Official Journal of the Japanese Circulation Society
Hiroyoshi MoriYoshikazu Nakaoka

Abstract

Pulmonary arterial hypertension (PAH), particularly connective tissue disease-associated PAH (CTD-PAH), is a progressive disease and novel therapeutic agents based on the specific molecular pathogenesis are desired. In the pathogenesis of CTD-PAH, inflammation, immune cell abnormality, and fibrosis play important roles. However, the existing mouse pulmonary hypertension (PH) models do not reflect these features enough. The relationship between inflammation and hypoxia is still unclear.Methods and Results:Intraperitoneal administration of pristane, a kind of mineral oil, and exposure to chronic hypoxia were combined, and this model is referred to as pristane/hypoxia (PriHx) mice. Hemodynamic and histological analyses showed that the PriHx mice showed a more severe phenotype of PH than pristane or hypoxia alone. Immunohistological and flow cytometric analyses revealed infiltration of immune cells, including hemosiderin-laden macrophages and activated CD4+helper T lymphocytes in the lungs of PriHx mice. Pristane administration exacerbated lung fibrosis and elevated the expression of fibrosis-related genes. Inflammation-related genes such asIl6andCxcl2were also upregulated in the lungs of PriHx mice, and interleukin (IL)-6 blockade...Continue Reading

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Citations

Feb 19, 2021·Circulation Journal : Official Journal of the Japanese Circulation Society·Toshihisa Anzai
Apr 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Takeshi MasakiYoshikazu Nakaoka
Mar 17, 2021·British Journal of Pharmacology·Joshua P DignamAdrian J Hobbs
Nov 25, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanjiang XingJun Yang

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