title: Uric Acid Induces Endothelial Dysfunction by Activating the HMGB1/RAGE Signaling Pathway.
abstract: 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 dysfunctionviathe HMGB1/RAGE signaling pathway.
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Department of Medical Genetics and Cell Biology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Department of Endocrinology and Metabolism, People's Hospital of Shangrao City, Shangrao, Jiangxi 334600, China.
authors.forename: Xi-Mei
authors.initials: XM
authors.lastname: Duan
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Yun-Liang
authors.initials: YL
authors.lastname: Tang
authors.affiliation: Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330003, China.
authors.forename: Ze-Lin
authors.initials: ZL
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Medical Genetics and Cell Biology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Ji-Xiong
authors.identifier: 0000-0002-4947-3576
authors.initials: JX
authors.lastname: Xu
mesh_terms: D002448:Cell Adhesion; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic; D024243:HMGB1 Protein / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction; D014527:Uric Acid / Q000737:chemistry*
chemical_list: C000593871:AGER protein, human; D016207:Cytokines; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D014527:Uric Acid; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III