Renin angiotensin (Ang) system (RAS) activation in metabolic syndrome (MS) patients is associated with elevated uric acid (UA) levels, resulting in endothelial system dysfunction. Our previous study demonstrated that excessive UA could cause endothelial injury through the aldose reductase (AR) pathway. This study is the first to show that a high concentration of Ang II in human umbilical vein endothelial cells (HUVECs) increases reactive oxygen species (ROS) components, including O₂^⋅- and H₂O₂, and further aggravates endothelial system injury induced by high UA (HUA). In a MS/hyperuricemia model, nitric oxide (NO) production was decreased, followed by a decrease in total antioxidant capacity (TAC), and the concentration of the endothelial injury marker von Willebrand factor (vWF) in the serum was increased. Treatment with catalase and polyethylene glycol covalently linked to superoxide dismutase (PEG-SOD) to individually remove H₂O₂ and O₂^⋅- or treatment with the AR inhibitor epalrestat decreased ROS and H₂O₂, increased NO levels and TAC, and reduced vWF release. Taken together, these data indicate that HUA and Ang II act additively to cause endothelial dysfunction via oxidative stress, and specific elimination of O₂^⋅- and H₂O₂ improves endothelial function. We provide theoretical evidence to prevent or delay endothelial injury caused by metabolic diseases.

中文翻译：

---

高浓度的尿酸和血管紧张素II会相加产生内皮损伤。

代谢综合征（MS）患者的肾素血管紧张素（Ang）系统（RAS）激活与尿酸（UA）水平升高有关，导致内皮系统功能异常。我们先前的研究表明，过量的UA可能通过醛糖还原酶（AR）途径引起内皮损伤。这项研究是首次表明，在人类的高浓度血管紧张素Ⅱ的脐静脉内皮细胞（HUVECs）的增加的活性氧物种（ROS）成分的，包括O- ₂ ^⋅-和H ₂ ö ₂，并进一步加重了由高UA（HUA）引起的内皮系统损伤。在MS /高尿酸血症模型中，一氧化氮（NO）的产生减少，然后总抗氧化能力（TAC）下降，并且血清中内皮损伤标记物von Willebrand因子（vWF）的浓度增加。治疗与过氧化氢酶和聚乙二醇共价连接于超氧化物歧化酶（PEG-SOD）单独除去H2S ₂ ö ₂和O ₂ ^⋅-或与AR抑制剂依帕司他治疗降低ROS和H ₂ ö ₂，增加NO水平和TAC并减少vWF释放。总之，这些数据表明，HUA和Ang II作用相加，以使通过氧化应激内皮功能障碍，和O的特异性清除₂ ^⋅-和H ₂ ö ₂改善内皮功能。我们提供了理论上的证据来预防或延缓由代谢疾病引起的内皮损伤。