Attenuation of pulmonary hypertension, but not emphysematous change, by breeding emphysema model mice at sea level

Masaki Fujita, Satoshi Ikegame, Qing Ye, Eiji Harada, Hiroshi Ouchi, Ichiro Inoshima, Kentaro Watanabe, Robert J. Mason, Yoichi Nakanishi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Tumor necrosis factor (TNF)-α is a key pro-inflammatory cytokine, thought to be important in the pathogenesis of pulmonary emphysema. TNF-α 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-α 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.

Original languageEnglish
Pages (from-to)286-292
Number of pages7
Issue number3
Publication statusPublished - Mar 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology


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