Uric Acid Promotes Human Umbilical Vein Endothelial Cell Senescence In Vitro.

BACKGROUND/OBJECTIVES: Uric acid can act as a prooxidant or an antioxidant; therefore, its effects on human umbilical vein endothelial cells (HUVECs) were investigated to better understand its role in promoting cellular senescence and vascular dysfunction. METHODS: HUVECs were exposed to different concentrations of exogenous uric acid levels typically found in patients with cardiovascular conditions (5 mg/dL, 7.5 mg/dL, and 10 mg/dL) to assess cell viability, proliferation, and senescence markers including SA-β-Gal activity, γ-H2A.X and 53BP1 expression, as well as mitochondrial dysfunction parameters such as reactive oxygen species (ROS) production, mitochondrial mass, and mitochondrial membrane potential (ΔΨm). Additionally, the secretion of factors related to the senescence-associated secretory phenotype (SASP) was quantified. RESULTS: Uric acid concentrations of 7.5 mg/dL and above significantly reduced HUVEC viability, enhanced proliferation, and increased markers of cellular senescence, including SA-β-Gal activity and γ-H2A.X/53BP1 expression. Higher uric acid levels also led to increased ROS production, increased mitochondrial mass, and reduced membrane potential. Uric acid also dose-dependently increased IL-6, IL-8, HGF, GRO-1, and TGF-β1 levels. CONCLUSIONS: High uric acid concentrations (≥7.5 mg/dL) promote HUVEC senescence, possibly due to ROS-induced DNA damage. In addition, uric acid triggers the production of pro-inflammatory cytokines and growth factors.