Center for Nephrology and Metabolomics and Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Nephrology, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong Province, China.
Clin Exp Nephrol. 2019 Sep;23(9):1100-1108. doi: 10.1007/s10157-019-01755-0. Epub 2019 Jun 18.
Patients 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.
Forearm 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.
Phlebosclerosis, 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.
Phlebosclerosis 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.
尿毒症患者心血管疾病（CVD）死亡率过高。动脉重塑主要负责尿毒症引起的 CVD，已得到充分研究，而静脉重塑则知之甚少。在此，我们研究了尿毒症患者静脉重塑的组织病理学和蛋白质组学特征。
在动静脉瘘手术期间从 9 名尿毒症患者的前臂头静脉中分离，在应用手术清创术时从 9 名健康对照者中分离。对苏木精-伊红、马松三色、冯·科萨和增殖细胞核抗原免疫组化染色进行组织病理学染色。进行等重标记相对和绝对定量（iTRAQ）蛋白质组学分析以探索静脉的蛋白质组。通过 Western blot、免疫组化和免疫荧光验证核心调控蛋白。
静脉中突出的病理表现是静脉内膜变薄和中膜增厚，伴血管平滑肌细胞（VSMC）无序增殖，这是尿毒症患者周围静脉的特征性表现，而炎症细胞浸润、动脉粥样硬化或钙化则不明显。iTRAQ 分析显示，与健康对照组相比，尿毒症患者静脉中 350 种蛋白明显改变，其中整合素-β1（ITGβ1）通过分子间相互作用网络分析显示出最强的调节能力。尿毒症患者前臂头静脉中 ITGβ1 表达增强主要与 VSMC 的无序增殖相关，而与血管内皮细胞相关较少。
静脉硬化是尿毒症患者周围静脉的突出病理表现。这种病理改变主要归因于 VSMC 的无序增殖，这可能是由 ITGβ1 介导的。
