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BioMed Research International
Volume 2017 (2017), Article ID 4391920, 11 pages
Research Article

Uric Acid Induces Endothelial Dysfunction by Activating the HMGB1/RAGE Signaling Pathway

1Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
2Department of Medical Genetics and Cell Biology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, China
3Department of Endocrinology and Metabolism, People’s Hospital of Shangrao City, Shangrao, Jiangxi 334600, China
4Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330003, China

Correspondence should be addressed to Ji-Xiong Xu

Received 3 July 2016; Revised 25 October 2016; Accepted 6 November 2016; Published 1 January 2017

Academic Editor: Senthil K. Venugopal

Copyright © 2017 Wei Cai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Uric acid (UA) is a risk factor for endothelial dysfunction, a process in which inflammation may play an important role. UA increases high mobility group box chromosomal protein 1 (HMGB1) expression and extracellular release in endothelial cells. HMGB1 is an inflammatory cytokine that interacts with the receptor for advanced glycation end products (RAGE), inducing an oxidative stress and inflammatory response, which leads to endothelial dysfunction. In this study, human umbilical vein endothelial cells (HUVECs) were incubated with a high concentration of UA (20 mg/dL) after which endothelial function and the expression of HMGB1, RAGE, nuclear factor kappa B (NF-κB), inflammatory cytokines, and adhesion molecules were evaluated. UA inhibited endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production in HUVECs, increased intracellular HMGB1 expression and extracellular HMGB1 secretion, and upregulated RAGE expression. UA also activated NF-κB and increased the level of inflammatory cytokines. Blocking RAGE significantly suppressed the upregulation of RAGE and HMGB1 and prevented the increase in DNA binding activity of NF-κB and the levels of inflammatory cytokines. It also blocked the decrease in eNOS expression and NO production induced by UA. Our results suggest that high concentrations of UA cause endothelial dysfunction via the HMGB1/RAGE signaling pathway.