Hoshikawa Yasushi, Nana-Sinkam Patrick, Moore Mark D, Sotto-Santiago Sylk, Phang Tzulip, Keith Robert L, Morris Kenneth G, Kondo Takashi, Tuder Rubin M, Voelkel Norbert F, Geraci Mark W
Pulmonary Hypertension Center, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Physiol Genomics. 2003 Feb 6;12(3):209-19. doi: 10.1152/physiolgenomics.00081.2001.
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.
不同动物物种对缺氧的反应各不相同。与大鼠相比，小鼠在长期暴露于缺氧环境后肺动脉增厚程度较轻。我们推测，缺氧大鼠的肺组织基因表达模式将不同于缺氧小鼠。我们将斯普拉格-道利大鼠和C57BL/6小鼠暴露于1周和3周的低压缺氧环境中。尽管两个物种都出现了肺动脉高压，但小鼠的肺血管重塑程度低于大鼠。微阵列基因分析表明，在缺氧条件下，小鼠和大鼠之间存在明显不同的基因表达模式。此外，一些基因在缺氧1周的较早时间点似乎反应更强烈。大鼠的缺氧条件会诱导参与内皮细胞增殖、抑制细胞凋亡和血管舒张的基因。暴露于缺氧条件下的小鼠会降低参与血管舒张和内皮细胞增殖的基因表达。虽然我们无法确定慢性缺氧期间基因的差异表达是肺血管重塑差异的原因还是结果，但我们认为，一组选择性基因的过表达和低表达之间的平衡可能是肺血管重塑和血管张力控制的原因。
