Allopurinol Attenuates Senescence and Oxidative Stress in Endothelial Cells Exposed to Serum from Hypertensive Patients with Hyperuricemia - a Pilot Study

Background/Aims: Endothelial cell senescence is a key contributor to the development of vascular pathologies, including arterial hypertension. Uric acid has been shown to promote oxidative stress and inflammation, thereby accelerating endothelial dysfunction and senescence. Although xanthine oxidase inhibition with allopurinol has demonstrated cardiovascular benefits, its effect on endothelial senescence remains insufficiently characterised. This study aimed to investigate the impact of sera from patients with arterial hypertension and elevated uric acid levels on the senescence of human umbilical vein endothelial cells, and to determine whether allopurinol treatment modulates this effect. Materials: In this study, human umbilical vein endothelial cells were cultured and exposed to sera from hypertensive patients with elevated uric acid levels (≥5 mg/dL) before and after six weeks of allopurinol treatment (300 mg/day). A control group consisting of healthy individuals with normal uric acid levels was established. Eighteen participants of both sexes were recruited to the study. Markers of senescence (SA-β-Gal, γ-H2A.X, 53BP1), oxidative stress (mitochondrial and cytosolic reactive oxygen species, mitochondrial mass, membrane potential), cell proliferation and inflammatory cytokine production were analysed. Results: Sera from hypertensive patients before treatment induced endothelial senescence and oxidative stress significantly and altered secretory profiles in endothelial cells compared to the controls; however, allopurinol treatment led to a partial reversal of these changes. Specifically, it reduced mitochondrial reactive oxygen species, mitochondrial mass and γ-H2A.X levels, and increased cell proliferation. However, not all markers returned to baseline values, and some (e.g. inflammatory mediators) remained elevated or even increased further after treatment. Conclusion: The findings demonstrate that allopurinol partially reverses uric acid- and hypertension-related endothelial senescence and oxidative damage. However, the incomplete normalisation suggests that multiple overlapping pathways contribute to vascular cell senescence in this context.