Histopathological and proteomic analyses identify integrin-beta 1 as a potential mediator of phlebosclerosis in uremic patients
Histopathological and proteomic analyses identify integrin-beta 1 as a potential mediator of phlebosclerosis in uremic patients
复制标题
组织病理学和蛋白质组学分析确定整合素-β1 是尿毒症患者静脉硬化的潜在介质
DOI：
10.1007/s10157-019-01755-0
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发表时间：
2019
影响因子：
2.3
通讯作者：
Peng Ai
中科院分区：
文献类型：
--
作者：
Zhou Chunyu;Li Changbin;Wang Qiang;Wu Mingyu;Mohan Ch;ra;Hu Dayong;Peng Ai
背景尿毒症患者因心血管疾病（CVD）而死亡率高.动脉重塑是尿毒症引起的CVD的主要原因，并且已经得到了很好的研究，但静脉重塑的了解甚少。在这里，我们调查尿毒症patients.MethodsForearm头静脉的静脉重塑的组织病理学和蛋白质组学概况分离从9个尿毒症患者在动静脉瘘手术，并从9个健康对照时，应用手术清创。苏木精-伊红、Masson三色、von Kossa和抗增殖细胞核抗原的免疫组织化学（IHC）染色进行组织病理学检查。执行相对和绝对定量（iTRAQ）蛋白质组分析的等压标签来探索静脉的蛋白质组。结果尿毒症患者外周静脉主要病理表现为静脉硬化（Phlebosclerosis），表现为内膜稀疏、中膜增厚、血管平滑肌细胞（VSMCs）增殖紊乱，而炎性细胞浸润、动脉粥样硬化及钙化不明显。iTRAQ分析显示，与健康对照相比，尿毒症患者静脉硬化中有350个蛋白质发生了显著变化，其中整合素β1（ITGβ1）的分子间相互作用网络分析显示其调控能力最强。尿毒症患者前臂头静脉ITGβ1表达增强主要与VSMCs的异常增殖共表达，与血管内皮细胞的异常增殖共表达较少。这种病理改变主要是由于VSMCs的增殖紊乱所致，而ITGβ1可能是VSMCs增殖紊乱的重要介导因子。
BackgroundPatients with uremia have an excessive mortality from cardiovascular disease (CVD). Arterial remodeling is mainly responsible for uremia-induced CVD and has been well studied, yet venous remodeling is poorly understood. Here we investigate the histopathology and proteomic profiles of venous remodeling in uremic patients.MethodsForearm cephalic veins were isolated from nine uremic patients during surgeries for arteriovenous fistula, and from nine healthy controls when applying surgical debridement. Hematoxylin–eosin, Masson’s trichrome, von Kossa, and immunohistochemistry (IHC) against proliferating cell nuclear antigen were stained for histopathology. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was executed to explore the proteome of the veins. The core regulatory protein was validated by western blot, IHC, and immunofluorescence.ResultsPhlebosclerosis, characterized by intimal rarefaction and medial thickening with disordered proliferation of vascular smooth muscle cells (VSMCs), was the prominent pathological manifestation of peripheral veins in uremic patients, while inflammatory cell infiltration, atherosclerosis or calcification were not obviously detected. iTRAQ analysis showed that 350 proteins were significantly changed in phlebosclerosis of uremic patients compared with healthy controls, of which integrin-β1 (ITGβ1) exhibited the strongest regulatory ability by intermolecular interaction network analysis. The enhanced ITGβ1 expression was mainly co-expressed with the disordered proliferation of VSMCs while a little with vascular endothelial cells in the forearm cephalic veins of uremic patients.ConclusionsPhlebosclerosis is the prominent pathological manifestation in peripheral veins of uremic patients. This pathological alteration mainly attributes to the disordered proliferation of VSMCs, which is potentially mediated by ITGβ1.