title: Attenuation of pulmonary hypertension, but not emphysematous change, by breeding emphysema model mice at sea level.
abstract: Tumor necrosis factor (TNF)-alpha is a key pro-inflammatory cytokine, thought to be important in the pathogenesis of pulmonary emphysema. TNF-alpha overexpression in the lung leads to the phenotypic features of pulmonary emphysema, pulmonary hypertension, and right ventricular hypertrophy in mice bred in Denver, 5240 feet/1600 m of altitude. This study hypothesized that the altitude could affect the development of pulmonary emphysema as well as pulmonary hypertension. To investigate the effect of the altitude, TNF-alpha transgenic mice were bred at sea level, Fukuoka, Japan. The pulmonary physiology and histology demonstrated similar development of pulmonary emphysema, compared to the mice bred in Denver. With respect to pulmonary hypertension, right ventricular hypertrophy was attenuated. Interestingly, mortality rate was significant lower in the mice bred at sea level. In contrast with the results in Denver, a significant decrease of vascular endothelial growth factor (VEGF) and its receptors expression was not found. From these data, we consider that the altitude affects development of pulmonary hypertension through the expression of VEGF and its receptors. In contrast, the effect of altitude was not clear regarding the development of pulmonary emphysema.
authors.affiliation: Research Institute for Diseases of Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. mfujita@fukuoka-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikegame
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Eiji
authors.initials: E
authors.lastname: Harada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ouchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Inoshima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mason
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000531:Altitude; D000818:Animals; D001947:Breeding; D004195:Disease Models, Animal; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor