The role of hyperuricemia on vascular endothelium dysfunction.

Abstract

Hyperuricemia appears to be associated with an increased risk for cardiovascular disease and associated mortality. Population epidemiological data support a causal link between hyperuricemia and cardiovascular disease. Endothelium injury could be one of the potential mechanisms in hyperuricemia-induced cardiovascular disease. However, the specific role of uric acid (UA) in the impairment of vascular relaxation and its signal transduction pathway has not been examined. The authors investigated the role of UA on vascular relaxation, nitric oxide (NO) production and expression of proinflammatory cytokines. Brachial flow-mediated dilation and nitroglycerine-mediated dilation were measured by B-mode ultrasound with 10 megahertz linear-array transducer from 21 patients with hyperuricemia and 16 control subjects. Human umbilical vein endothelial cells (ECs) were incubated with UA (5-15 mg/dl) with or without nuclear factor (NF)-κB inhibitor II. Hyperuricemia inhibited brachial flow-mediated dilation. While UA significantly inhibited NO expression with time course- and dose- dependent manner in the cultured ECs, 10 mg/dl UA also increased expression of inflammation cytokine interleukin (IL)-6, IL-8 and tumor necrosis factor-α in vitro. These abnormalities were associated with UA-induced activation of transcription factor NF-κB. Furthermore, NF-κB inhibitor II prevented UA-induced reduction of NO and increased inflammation cytokines. These data suggested hyperuricemia-induced endothelium injury and vascular dysfunction by a reduction of NO and expression of inflammatory cytokines through the NF-κB pathway.