Proteomic Analysis of Lung Tissues From Patients With Pulmonary Arterial Hypertension
Proteomic Analysis of Lung Tissues From Patients With Pulmonary Arterial Hypertension
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DOI：
10.1161/circulationaha.110.972745
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发表时间：
2010-11-16
期刊：
影响因子：
37.8
通讯作者：
Wilkins, Martin R.
中科院分区：
文献类型：
--
作者：
Abdul-Salam, Vahitha B.;Wharton, John;Wilkins, Martin R.
背景--肺动脉高压是一种血管重塑障碍，导致肺血流阻力增加。为了进一步了解肺动脉高压患者肺组织中蛋白质的表达情况，我们采用无偏倚的方法研究了肺组织中蛋白质的表达。方法与结果：采用无标记液相色谱串联质谱技术，比较了8例肺动脉高压患者和8例正常对照肺组织中蛋白质的表达。检测到了300多种蛋白质。根据可靠的标准，25种蛋白质的水平在两组之间存在差异。大多数上调蛋白与细胞生长、增殖和细胞代谢有关。新的发现包括细胞内氯离子通道4、晚期糖基化终产物受体和Periostin的表达增加。Western blotting证实，参与血管生成的多功能蛋白氯离子细胞内通道4和参与肺动脉高压的几个信号通路-转化生长因子-β、血管内皮生长因子和骨形态发生蛋白的表达增加，并主要定位于闭塞性和丛状血管病变的内皮细胞。结论非标记蛋白质组学证实了几种蛋白在肺动脉高压肺组织中的表达差异，其中许多与疾病过程有关。细胞内氯离子通道4表达增加可能与丛状病变血管生成紊乱有关。(发行量。2010年；122：2058-2067。)
Background-Pulmonary arterial hypertension is a disorder of vascular remodeling causing increased resistance to pulmonary blood flow. The expression of proteins in lungs from pulmonary arterial hypertension patients was investigated in an unbiased approach to further understand the pathobiology of this disease.Methods and Results-Label-free liquid chromatography tandem mass spectrometry was used to compare protein profiles in surgical samples of lungs from 8 patients with pulmonary arterial hypertension and 8 control subjects. More than 300 proteins were detected. On the basis of robust criteria, the levels of 25 proteins varied between the 2 groups. The majority of upregulated proteins were associated with cell growth, proliferation, and cell metabolism. Novel findings included an increased expression of chloride intracellular channel 4, receptor for advanced glycation end products, and periostin. Increased expression of chloride intracellular channel 4, a multifunctional protein involved in angiogenesis, and several signaling pathways implicated in pulmonary arterial hypertension-transforming growth factor-beta, vascular endothelial growth factor, and bone morphogenetic protein-was confirmed by Western blotting and localized predominantly to endothelial cells in occlusive and plexiform vascular lesions.Conclusions-Label-free proteomics identified differences in the expression of several proteins in the pulmonary arterial hypertension lung, many of which are relevant to the disease process. Increased expression of chloride intracellular channel 4 may be pertinent to the disorganized angiogenesis of plexiform lesions. (Circulation. 2010; 122: 2058-2067.)