Mechanisms of hypoxia-induced transformation in endothelial cells

MCT诱导的肺动脉显示与匹莫硝唑结合，这是一种缺氧检测剂，与包括肺上皮细胞在内的血管壁周围区域的缺氧区域结合。与对照组相比，HIF-1β+/-组小鼠肺泡巨噬细胞的重量指数明显减轻，右、左室间隔重量比明显降低，肺血管数目明显增加，中膜厚度指数显著降低。巨噬细胞集落刺激因子治疗的HIF-1β+/-小鼠的肌化肺动脉数目较对照组明显减少。此外，有趣的是，给予内皮素受体阻滞剂波生坦可以改善野生型小鼠的PAH，达到与HIF-1β+/-小鼠相同的水平。提示MCT诱导的血管内皮细胞缺氧诱导因子-1β参与了肺动脉高压的发生发展。

MCT-induced pulmonary arteries demonstrated binding of pimonidazole, a hypoxia detection agent that binds to regions of hypoxia in the region around vascular walls including lung epithelial cells. Indices of the PAH were significantly alleviated in the Hif-1β+/-mice compared to the control as the following data showed ; the weight ratio of right ventricular to left ventricular with septum was significantly decreased ; the number of pulmonary arteries was significantly increased ; indices of the medial thickness was significantly decreased. The number of musculized pulmonary arteries in MCT-treated Hif-1β+/-mice was significantly decreased compared to that of the control mice. In addition, interestingly, the PAH in wild type mice was ameliorated by administration of bosentan, an endothelin receptor blocker, to the same level of that in Hif-1β+/-mice. These results indicate that the development of MCT-induced PAH was mediated by HIF-1βin endothelial cells.