Work

Uratylated albumin activates endothelial cells to induce monocyte adhesion and the release of pro-inflammatory cytokines

Year: 2026

Type: article

Abstract: Albumin, the most abundant serum protein in mammals, is critical for transporting low-water-soluble metabolites, ions, and xenobiotics, as well as maintaining osmotic balance. This protein is highly susceptible to post-translational modifications, which can alter its structure and function. Reactive oxygen species (ROS) play a significant role in inducing such modifications, leading to protein dysfunction and contributing to inflammatory and cardiovascular pathologies. Previous studies have demonstrated a link between uric acid (UA) oxidation products, particularly urate hydroperoxide (HOOU), and albumin modifications through a process termed uratylation. These albumin adducts result from the addition of a 140 Da product mass predominantly on lysine and amine from N-terminal residues. Therefore, the aim of this study was to investigate the structural and functional consequences of uratylation on albumin and its effects on endothelial cells. Uratylation promotes a decrease in enthalpy change of denaturation of albumin, total λ 280 nm absorption and binding of Anilino-Naphthalene-Sulfonic acid (ANS), suggesting slight changes in protein structure. Uratylated albumin reduced human umbilical vein endothelial cell (HUVEC) migration, increased intercellular adhesion molecule-1 (ICAM-1) expression and, consequently, monocyte adhesion (THP-1), indicating endothelial activation. Furthermore, the presence of uratylated albumin stimulated the release of tumor necrosis factor-α (TNF-α). These findings provide novel insights into the mechanistic pathways connecting uric acid oxidation, post-translational modification on albumin, and inflammation, highlighting the potential role of uratylated albumin in endothelial dysfunction and atherogenesis. • Uratylation, a novel post translational modification on lysine residues, affects albumin structure • Uratylated albumin impairs HUVEC migration, increases ICAM-1 expression, and promotes monocyte adhesion • Endothelial cell activation by uratylated albumin reveals an unprecedented described mechanism for the contribution of UA oxidation in endothelial dysfunction.

Source: Redox Biochemistry and Chemistry

DOI: 10.1016/j.rbc.2026.100071