Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension
Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension
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DOI：
10.1378/chest.129.3.696
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发表时间：
2006-03-01
期刊：
影响因子：
9.6
通讯作者：
Cool, CD
中科院分区：
文献类型：
--
作者：
Achcar, ROD;Demura, Y;Cool, CD
小泡是细胞质膜微域，参与组织和聚集许多信号分子。在肺中，小泡存在于内皮细胞、平滑肌、成纤维细胞和肺细胞中。小窝蛋白是小窝的主要结构蛋白。小窝蛋白I在转化细胞中下调，可能是一种肿瘤抑制蛋白。小窝蛋白2与小窝蛋白1共表达并异聚。由于严重肺动脉高压（PH）的丛状病变细胞发生表型改变，我们想知道这些细胞是否缺乏小窝蛋白。我们现在通过免疫定位证明，虽然小泡蛋白在肺内皮细胞、平滑肌细胞和肺泡间隔细胞中表达，但在丛状病变和一些肌肉化的毛细血管前小动脉中，其表达不存在或减少。相比之下，对严重PH患者的总肺提取物进行Western blot分析显示，小窝蛋白没有明显减少。与人肺组织类似，严重PH大鼠模型显示复杂血管病变中小泡蛋白表达缺失或降低。此外，由于HO-1在血管病变中的表达与小窝蛋白的表达相似，小窝蛋白和血红素加氧酶1 （HO-1，一种热休克蛋白）似乎是共表达的。我们认为，在严重PH下，复杂血管病变细胞中小窝蛋白表达的缺失反映了这些细胞的增殖和抗凋亡性质。
Caveolae are cell plasma membrane microdomains implicated in organizing and concentrating many signaling molecules. In the lung, caveolae are in endothelium, smooth muscle, fibroblasts, and pneumocytes. Caveolin is the main structural protein of caveolae. Caveolin I is down-regulated in transformed cells and may be a tumor suppressor protein. Caveolin 2 is coexpressed and hetero-oligomerizes with caveolin 1. Because the cells of the plexiform lesions in severe pulmonary hypertension (PH) are phenotypically altered, we wondered whether these cells lack caveolin. We now demonstrate by immunolocalization that while caveolin is expressed in lung endothelial, smooth-muscle, and alveolar septal cells, its expression is absent or decreased in plexiform lesions and in some muscularized precapillary arterioles. in contrast, Western blot analysis of total lung extracts from patients with severe PH shows no significant reduction in caveolin. Similar to the human lung tissue, a rat model of severe PH demonstrates absent-to-decreased caveolin expression in the complex vascular lesions. Additionally, it appears that caveolin and heme oxygenase 1 (HO-1) [a heat shock protein] are co-expressed since HO-1 expression parallels caveolin expression in vascular lesions. We propose that loss of caveolin expression in the cells of the complex vascular lesions in severe PH reflects the proliferating and apoptosis-resistant nature of these cells.