PMID- 12743010
OWN - NLM
STAT- MEDLINE
DCOM- 20030627
LR  - 20220409
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 41
IP  - 6
DP  - 2003 Jun
TI  - Uric acid stimulates monocyte chemoattractant protein-1 production in vascular 
      smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2.
PG  - 1287-93
AB  - Previous studies have reported that uric acid stimulates vascular smooth muscle 
      cell (VSMC) proliferation in vitro. We hypothesized that uric acid may also have 
      direct proinflammatory effects on VSMCs. Crystal- and endotoxin-free uric acid 
      was found to increase VSMC monocyte chemoattractant protein-1 (MCP-1) expression 
      in a time- and dose-dependent manner, peaking at 24 hours. Increased mRNA and 
      protein expression occurred as early as 3 hours after uric acid incubation and 
      was partially dependent on posttranscriptional modification of MCP-1 mRNA. In 
      addition, uric acid activated the transcription factors nuclear factor-kappaB and 
      activator protein-1, as well as the MAPK signaling molecules ERK p44/42 and p38, 
      and increased cyclooxygenase-2 (COX-2) mRNA expression. Inhibition of p38 (with 
      SB 203580), ERK 44/42 (with UO126 or PD 98059), or COX-2 (with NS398) each 
      significantly suppressed uric acid-induced MCP-1 expression at 24 hours, 
      implicating these pathways in the response to uric acid. The ability of both 
      n-acetyl-cysteine and diphenyleneionium (antioxidants) to inhibit uric 
      acid-induced MCP-1 production suggested involvement of intracellular redox 
      pathways. Uric acid regulates critical proinflammatory pathways in VSMCs, 
      suggesting it may have a role in the vascular changes associated with 
      hypertension and vascular disease.
FAU - Kanellis, John
AU  - Kanellis J
AD  - Division of Nephrology, Baylor College of Medicine, SM-1273, 6550 Fannin St, 
      Houston TX 77030. rjohnson@bcm.tmc.edu
FAU - Watanabe, Susumu
AU  - Watanabe S
FAU - Li, Jin H
AU  - Li JH
FAU - Kang, Duk Hee
AU  - Kang DH
FAU - Li, Ping
AU  - Li P
FAU - Nakagawa, Takahiko
AU  - Nakagawa T
FAU - Wamsley, Ann
AU  - Wamsley A
FAU - Sheikh-Hamad, David
AU  - Sheikh-Hamad D
FAU - Lan, Hui Y
AU  - Lan HY
FAU - Feng, Lili
AU  - Feng L
FAU - Johnson, Richard J
AU  - Johnson RJ
LA  - eng
GR  - 1P50DK-064233-01/DK/NIDDK NIH HHS/United States
GR  - HL 68607/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030512
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Chemokine CCL2)
RN  - 0 (Isoenzymes)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 268B43MJ25 (Uric Acid)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Cyclooxygenase 2
MH  - Gene Expression Regulation
MH  - Isoenzymes/genetics/*physiology
MH  - Mitogen-Activated Protein Kinase 1/physiology
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - Muscle, Smooth, Vascular/drug effects/enzymology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Oxidation-Reduction
MH  - Prostaglandin-Endoperoxide Synthases/genetics/*physiology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Transcription Factor AP-1/metabolism
MH  - Up-Regulation
MH  - Uric Acid/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2003/05/14 05:00
MHDA- 2003/06/28 05:00
CRDT- 2003/05/14 05:00
PHST- 2003/05/14 05:00 [pubmed]
PHST- 2003/06/28 05:00 [medline]
PHST- 2003/05/14 05:00 [entrez]
AID - 01.HYP.0000072820.07472.3B [pii]
AID - 10.1161/01.HYP.0000072820.07472.3B [doi]
PST - ppublish
SO  - Hypertension. 2003 Jun;41(6):1287-93. doi: 10.1161/01.HYP.0000072820.07472.3B. 
      Epub 2003 May 12.