Febuxostat Attenuates the Induction of Vascular Cell Adhesion Protein 1 by TNF-α in Human Umbilical Vein Endothelial Cells

In a randomized trial, higher all-cause and cardiovascular mortality was observed in treatment with febuxostat than with allopurinol in patients with coexisting gout and serious cardiovascular conditions. In this study, we focus on an intervention of febuxostat or allopurinol as an anti-inflammatory treatment to reduce the transcription of nuclear factor-kappa B (NF-kappa B) and production of relevant inflammatory factors. We evaluated the effect of febuxostat on vascular cell adhesion protein 1 (VCAM-1) induction in cultured human umbilical vein endothelial cells (HUVECs). Cells were exposed to tumor necrosis factor (TNF)-alpha (10 ng/mL) treatment for 24 h. Febuxostat or allopurinol (0.1-100 mu M) was added to the bath medium 15 min before TNF-alpha treatment. VCAM-1 levels in HUVECs increased after 24-h TNF-alpha treatment (n = 4). Febuxostat and allopurinol significantly suppressed VCAM-1 induced by treatment with TNF-alpha in a dose-dependent manner (p < 0.05, n = 4). Furthermore, these drugs suppressed the NF-kappa B protein levels in the nucleus 4 h after TNF-alpha treatment (n = 3 or 4). Our results suggest that TNF-alpha induces VCAM-1 production via NF-kappa B, which can be blocked by febuxostat or allopurinol. The effect of febuxostat treatment on cardiovascular events may be associated with protection against the infiltration of lymphocytes or monocytes through VCAM-1 induction in inflamed endothelial cells such as arterial sclerosis.