Sun Jia Teng, Yang Ke, Lu Lin, Zhu Zheng Bin, Zhu Jin Zhou, Ni Jing Wei, Han Hui, Chen Nan, Zhang Rui Yan
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Cardiovascular Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; and.
Am J Physiol Renal Physiol. 2016 Mar 15;310(6):F511-7. doi: 10.1152/ajprenal.00508.2015. Epub 2016 Jan 13.
It is thought that carbamylated modification plays a crucial role in the development and progression of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). However, information on the biological effects of carbamylated high-density lipoprotein (C-HDL) in ESRD is poor. The present study investigated the carbamylation level of HDL in ESRD and the effects of C-HDL on endothelial repair properties. HDL was isolated from healthy control subjects (n = 22) and patients with ESRD (n = 30). The carbamylation level of HDL was detected using ELISA. Isolated C-HDL for use in tissue culture experiments was carbamylated in vitro to a similar extent to that observed in ESRD. Human arterial endothelial cells were treated with C-HDL or native HDL to assess their migration, proliferation, and angiogenesis properties. HDL-associated paraoxonase 1 activity was also determined by spectrophotometry assay. Compared with healthy control subjects, the carbamylation level of HDL in ESRD patients was increased and positively correlated with blood urea concentration. In vitro, C-HDL significantly inhibited migration, angiogenesis, and proliferation in endothelial cells. Mechanistic studies revealed that HDL-associated paraoxonase 1 activity was decreased and negatively correlated with the carbamylation level of HDL in ESRD patients. In addition, C-HDL suppressed the expression of VEGF receptor 2 and scavenger receptor class B type I signaling pathways in endothelial cells. In conclusion, the present study identified a significantly increased carbamylation level of HDL in ESRD. Furthermore, C-HDL inhibited endothelial cell repair functions.
据认为，氨甲酰化修饰在终末期肾病（ESRD）患者心血管疾病（CVD）的发生和发展中起关键作用。然而，关于氨甲酰化高密度脂蛋白（C-HDL）在ESRD中的生物学效应的信息却很少。本研究调查了ESRD中HDL的氨甲酰化水平以及C-HDL对内皮修复特性的影响。从健康对照者（n = 22）和ESRD患者（n = 30）中分离HDL。使用酶联免疫吸附测定法检测HDL的氨甲酰化水平。用于组织培养实验的分离的C-HDL在体外进行氨甲酰化，其程度与在ESRD中观察到的相似。用人动脉内皮细胞用C-HDL或天然HDL处理，以评估其迁移、增殖和血管生成特性。还通过分光光度法测定HDL相关的对氧磷酶1活性。与健康对照者相比，ESRD患者中HDL的氨甲酰化水平升高，且与血尿素浓度呈正相关。在体外，C-HDL显著抑制内皮细胞的迁移、血管生成和增殖。机制研究表明，ESRD患者中HDL相关的对氧磷酶1活性降低，且与HDL的氨甲酰化水平呈负相关。此外，C-HDL抑制内皮细胞中VEGF受体2和B类I型清道夫受体信号通路的表达。总之，本研究发现ESRD中HDL的氨甲酰化水平显著升高。此外，C-HDL抑制内皮细胞修复功能。
