Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers - Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth
Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers - Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth
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DOI：
10.1016/s0002-9440(10)65137-1
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发表时间：
1999-08-01
影响因子：
6
通讯作者：
Tuder, RW
中科院分区：
文献类型：
--
作者：
Cool, CD;Stewart, JS;Tuder, RW
重度肺动脉高压（PH）的丛状病变是主要由内皮细胞组成的复杂血管结构。在这项研究中，我们使用免疫组化标记来识别肺血管的各种细胞层，并确定不同的内皮细胞表型在肺动脉严重PH的影响。我们的计算机三维重建的9个血管在Eve患者严重PH表明，丛状（n = 14）和隐匿性闭塞（n = 6）病变发生远端的小肺动脉的分支点。而且，丛状病变以孤立性病变发生，而同心性闭塞性病变似乎仅与丛状结构相关并接近丛状结构。丛状病变的内皮细胞强烈且均匀地表达血管内皮生长因子（VEGF）受体KDR，并在丛状病变的中心核心和邻近初始血管形成的外周区域中分离成细胞周期蛋白激酶抑制剂p27/kip 1阴性细胞和p27/kip 1阳性细胞。利用免疫组织化学和三维重建技术，我们发现丛状病变是动态的血管结构，其特征在于至少有两种内皮细胞表型。丛状动脉病不仅仅是一个终末期或血栓形成后的变化，它可能代表一个正在进行的，血管生成内皮细胞生长过程中的一个阶段。
The plexiform lesions of severe pulmonary hypertension (PH) are complex vascular structures composed primarily of endothelial cells. In this study, we use immunohistochemical markers to identify the various cell layers of pulmonary vessels and to identify different endothelial cell phenotypes in pulmonary arteries affected by severe PH. Our computerized three-dimensional reconstructions of nine vessels in Eve patients with severe PH demonstrate that plexiform (n = 14) and conceatric-obliterative (n = 6) lesions occur distal to branch points of small pulmonary arteries. And, whereas plexiform lesions occur as solitary lesions, concentric-obliterative lesions appear to be only associated with, and proximal to, plexiform structures. The endothelial cells of plexiform lesions express intensely and uniformly the vascular endothelial growth factor (VEGF) receptor KDR and segregate phenotypically into cyclin-kinase inhibitor p27/kip1-negative cells in the central core of the plexiform lesion and p27/kip1-positive cells in peripheral areas adjacent to incipient blood vessel formation. Using immunohistochemistry and three-dimensional reconstruction techniques, we show that plexiform lesions are dynamic vascular structures characterized by at least two endothelial cell phenotypes. Plexiform arteriopathy is not merely an end stage or postthrombotic change-it may represent one stage in an ongoing, angiogenic endothelial cell growth process.