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Hypoxia induces different genes in the lungs of rats compared with mice

¹ Pulmonary Hypertension Center
² Division of Pulmonary Sciences and Critical Care Medicine
³ Cardiovascular Pulmonary Research Laboratory
⁴ Department of Pathology
⁵ Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262
⁶ Department of Thoracic Surgery, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan 980-8575

Different animal species have a varying response to hypoxia. Mice develop less pulmonary artery thickening after chronic hypoxia exposure than rats. We hypothesized that the lung tissue gene expression pattern displayed in hypoxic rats would differ from that of hypoxic mice. We exposed Sprague-Dawley rats and C57BL/6 mice to both 1 and 3 wk of hypobaric hypoxia. Although both species developed pulmonary hypertension, mice showed less pulmonary vascular remodeling than rats. Microarray gene analysis demonstrated a distinct pattern of gene expression between mice and rats when exposed to hypoxic conditions. In addition, some genes appeared to be more responsive at an earlier time point of 1 wk of hypoxia. Hypoxic conditions in the rat induce genes involved in endothelial cell proliferation, repression of apoptosis, and vasodilation. Mice exposed to hypoxic conditions decrease the expression of genes involved in vasodilation and in endothelial cell proliferation. Although we cannot determine whether the differential expression of genes during chronic hypoxia is cause or consequence of the differential pulmonary vascular remodeling, we propose that a balance between over- and under-expression of a selective group of genes may be responsible for lung vascular remodeling and vascular tone control.

pulmonary hypertension; chronic hypoxia; pulmonary vascular remodeling; gene microarray analysis; species differences

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