PMID- 28116308
OWN - NLM
STAT- MEDLINE
DCOM- 20170320
LR  - 20220316
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2017
DP  - 2017
TI  - Uric Acid Induces Endothelial Dysfunction by Activating the HMGB1/RAGE Signaling 
      Pathway.
PG  - 4391920
LID - 10.1155/2017/4391920 [doi]
LID - 4391920
AB  - 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-kappaB), 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-kappaB 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-kappaB 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.
FAU - Cai, Wei
AU  - Cai W
AD  - 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.
FAU - Duan, Xi-Mei
AU  - Duan XM
AD  - 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.
FAU - Liu, Ying
AU  - Liu Y
AD  - Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Yu, Jiao
AU  - Yu J
AD  - Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Tang, Yun-Liang
AU  - Tang YL
AD  - Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Liu, Ze-Lin
AU  - Liu ZL
AD  - Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of 
      Nanchang University, Nanchang, Jiangxi 330003, China.
FAU - Jiang, Shan
AU  - Jiang S
AD  - Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Zhang, Chun-Ping
AU  - Zhang CP
AD  - Department of Medical Genetics and Cell Biology, Medical College of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Liu, Jian-Ying
AU  - Liu JY
AD  - Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
FAU - Xu, Ji-Xiong
AU  - Xu JX
AUID- ORCID: 0000-0002-4947-3576
AD  - Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China.
LA  - eng
PT  - Journal Article
DEP - 20170101
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (AGER protein, human)
RN  - 0 (Cytokines)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 268B43MJ25 (Uric Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Cell Adhesion
MH  - Cytokines/metabolism
MH  - Endothelium, Vascular/metabolism/*physiopathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Gene Expression Regulation, Enzymologic
MH  - HMGB1 Protein/*metabolism
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Inflammation
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/antagonists & inhibitors/metabolism
MH  - Nitric Oxide Synthase Type III/antagonists & inhibitors/metabolism
MH  - Oxidative Stress/drug effects
MH  - Receptor for Advanced Glycation End Products/*metabolism
MH  - Signal Transduction
MH  - Uric Acid/*chemistry
PMC - PMC5237466
COIS- The authors declare that they have no conflict of interests.
EDAT- 2017/01/25 06:00
MHDA- 2017/03/21 06:00
PMCR- 2017/01/01
CRDT- 2017/01/25 06:00
PHST- 2016/07/03 00:00 [received]
PHST- 2016/10/25 00:00 [revised]
PHST- 2016/11/06 00:00 [accepted]
PHST- 2017/01/25 06:00 [entrez]
PHST- 2017/01/25 06:00 [pubmed]
PHST- 2017/03/21 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.1155/2017/4391920 [doi]
PST - ppublish
SO  - Biomed Res Int. 2017;2017:4391920. doi: 10.1155/2017/4391920. Epub 2017 Jan 1.