Emphysema Is-at the Most-Only a Mild Phenotype in the Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension.
American journal of respiratory and critical care medicine
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Bogaard, H. J., Legchenko, E., Chaudhary, K. R., Sun, X., Stewart, D. J., & Hansmann, G. (2019). Emphysema Is-at the Most-Only a Mild Phenotype in the Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension.. American journal of respiratory and critical care medicine, 200 (11), 1447-1450. https://doi.org/10.1164/rccm.201906-1200le
Translational research is essential to develop strategies for the treatment of pulmonary arterial hypertension (PAH) using animal models which reproduce the severity, the progressive nature and resistance to treatment of human PAH, including severe arterial remodeling and progressive right ventricular (RV) failure. We read with interest the letter by Kojonazariov et al. who propose to have found “severe emphysema in the SU5416/Hypoxia (SuHx) rat model of pulmonary hypertension”. The authors report that Wistar-Kyoto rats exposed to the combination of VEGFR2 inhibition by SU5416 and chronic hypoxia had moderately increased RVSP and RV mass compared to normoxic untreated animals. They applied in vivo micro-computed tomography (CT) to demonstrate an increase in lung volume and decreased lung density, an unaltered amount of lung tissue, but an increased air-to-tissue ratio, and claim these findings were confirmed by histological analysis, including mean linear intercept as surrogate of emphysema. Indeed, SU5416 has been previously shown to induce emphysema in normoxia, but this required repetitive SU5416 dosing (3 times weekly over 3 weeks) and occurred more predominantly in rats younger than 4 weeks of age (Norbert Voelkel, personal communication). In addition, emphysema could be negated, at the cost of the development of severe angioproliferative hypertension, by concomitant exposure to hypoxia.
Animals, Rats, Hypertension, Pulmonary, Emphysema, Pyrroles, Indoles, Phenotype, Hypoxia, Pulmonary Arterial Hypertension
European Commission / European Respiratory Society (ERS) Marie Sklodowska-Curie Postdoctoral Research Fellowships (RESPIRE) (R3201800-00506)
External DOI: https://doi.org/10.1164/rccm.201906-1200le
This record's URL: https://www.repository.cam.ac.uk/handle/1810/299068
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