Table8_Comprehensive proteomics of monocytes indicates oxidative imbalance functionally related to inflammatory response in chronic kidney disease-related atherosclerosis.XLSX

Atherosclerosis-induced cardiovascular events are the leading cause of mortality in chronic kidney disease (CKD) patients. Monocytes are involved in the formation of atherosclerotic plaques and mediate in the overproduction of ROS, promoting inflammation and oxidative stress. However, the relationship between monocytes, inflammation, and oxidative status in CKD-associated atherosclerosis has not been thoroughly investigated. Monocytes and plasma derived from two groups of CKD patients with varying degrees of atherosclerosis and two groups of patients with cardiovascular disease (CVD) and non-CKD atherosclerosis were analyzed. This study was designed to perform a comprehensive proteomic analysis of monocytes in combination with functional bioinformatics. In addition, a targeted investigation of oxidative stress- and inflammatory-related factors to explore CKD-associated atherosclerosis was applied. Dysregulation of proteins involved in lipid oxidation, cell survival, ROS synthesis and metabolism, and inflammatory responses has been revealed. The characteristic disturbances in the monocyte proteome changed with the progression of CKD. A closer examination of oxidative stress’s triggers, mediators, and effects on protein and lipid levels showed alterations in the oxidative imbalance between CKD and CVD. CKD monocytes demonstrated a significant increase of oxidized glutathione without changing the level of its reduced form. Evaluation of enzymatic antioxidants, sources of ROS, and modifications caused by ROS also revealed significant alterations between the study groups. In CKD, inflammation and oxidative imbalance correlated and drove each other. However, in CVD, oxidative stress-related factors were associated with each other but not to inflammatory proteins. Moreover, lipid abnormalities were more specific to classical CVD and unrelated to CKD. Such a comprehensive characterization of monocytes and oxidative stress in CKD and CVD patients has never been presented so far. Obtained results support the involvement of distinct mechanisms underlying the acceleration of atherosclerotic and non-atherosclerotic CKD.

动脉粥样硬化引发的 cardiovascular 事件是慢性肾脏病（CKD）患者死亡的首要原因。单核细胞参与动脉粥样硬化斑块的生成，并介导活性氧（ROS）的过量产生，从而促进炎症和氧化应激。然而，单核细胞、炎症和氧化状态在 CKD 相关动脉粥样硬化之间的关联尚未得到全面研究。本研究分析了两组不同程度动脉粥样硬化的 CKD 患者的单核细胞和血浆，以及两组心血管疾病（CVD）和非 CKD 动脉粥样硬化患者。本研究旨在对单核细胞进行全面的蛋白质组学分析，并结合功能生物信息学。此外，本研究还针对氧化应激和炎症相关因素进行了定向研究，以探索 CKD 相关的动脉粥样硬化。研究发现，参与脂质氧化、细胞存活、ROS 合成与代谢以及炎症反应的蛋白质失调。随着 CKD 的进展，单核细胞蛋白质组的特征性紊乱发生改变。对氧化应激的触发因素、介质及其对蛋白质和脂质水平的影响的深入考察，揭示了 CKD 与 CVD 之间氧化失衡的改变。CKD 单核细胞表现出氧化型谷胱甘肽的显著增加，而其还原型水平未变。对酶促抗氧化剂、ROS 来源以及 ROS 引起的修饰的评估，也揭示了研究组之间的显著差异。在 CKD 中，炎症和氧化失衡相互关联并相互驱动。然而，在 CVD 中，与氧化应激相关的因素相互关联，但并不与炎症蛋白相关。此外，脂质异常更特异地与经典 CVD 相关，而与 CKD 无关。如此全面地描述 CKD 和 CVD 患者的单核细胞和氧化应激，迄今为止尚无先例。所获得的结果支持了不同机制在 CKD 动脉粥样硬化和非动脉粥样硬化加速中的作用。