PMID- 16113518
OWN - NLM
STAT- MEDLINE
DCOM- 20051222
LR  - 20220228
IS  - 0250-8095 (Print)
IS  - 0250-8095 (Linking)
VI  - 25
IP  - 5
DP  - 2005 Sep-Oct
TI  - Uric acid causes vascular smooth muscle cell proliferation by entering cells via 
      a functional urate transporter.
PG  - 425-33
AB  - BACKGROUND: Soluble uric acid stimulates vascular smooth muscle cell (VSMC) 
      proliferation by activating mitogen-activated protein kinases, and stimulating 
      COX-2 and PDGF synthesis. The mechanism by which uric acid enters the VSMC is not 
      known. We hypothesized that uric acid enters via transporters similar to that 
      observed in the kidney. METHODS: We studied the uptake of uric acid into rat VSMC 
      under polarized and depolarized conditions and in the presence of organic anion 
      transport (OAT) inhibitors (probenecid and benzbromarone) or p-aminohippurate 
      (PAH). We also examined the ability of probenecid to inhibit uric acid-induced 
      VSMC proliferation and monocyte chemoattractant protein-1 (MCP-1) synthesis. 
      RESULTS: (14)C-Urate uptake was shown in VSMC and was enhanced under depolarized 
      conditions. (14)C-Uric acid uptake was inhibited by probenecid and benzbromarone, 
      as well as by unlabelled urate and PAH. Probenecid blocked VSMC proliferation and 
      MCP-1 expression in response to uric acid. VSMC did not express rOAT1-3, rOAT-5 
      or URAT-1 mRNA by PCR, but did express the voltage-sensitive transporter (UAT) by 
      both PCR and RNase protection assay. CONCLUSIONS: Urate enters VSMC by both 
      voltage-sensitive and OAT pathways, and the uptake, cell proliferation and MCP-1 
      expression can be blocked by OAT inhibitors. The specific transporter(s) 
      responsible for the urate uptake remains to be determined.
CI  - Copyright (c) 2005 S. Karger AG, Basel.
FAU - Kang, Duk-Hee
AU  - Kang DH
AD  - Division of Nephrology, Ewha Women's University College of Medicine, Seoul, 
      Korea.
FAU - Han, Lin
AU  - Han L
FAU - Ouyang, Xiaosen
AU  - Ouyang X
FAU - Kahn, Andrew M
AU  - Kahn AM
FAU - Kanellis, John
AU  - Kanellis J
FAU - Li, Ping
AU  - Li P
FAU - Feng, Lili
AU  - Feng L
FAU - Nakagawa, Takahiko
AU  - Nakagawa T
FAU - Watanabe, Susumu
AU  - Watanabe S
FAU - Hosoyamada, Makoto
AU  - Hosoyamada M
FAU - Endou, Hitoshi
AU  - Endou H
FAU - Lipkowitz, Michael
AU  - Lipkowitz M
FAU - Abramson, Ruth
AU  - Abramson R
FAU - Mu, Wei
AU  - Mu W
FAU - Johnson, Richard J
AU  - Johnson RJ
LA  - eng
GR  - I01 BX002586/BX/BLRD VA/United States
GR  - 1P50 DK 064233-01/DK/NIDDK NIH HHS/United States
GR  - R01 HL 68607/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050819
PL  - Switzerland
TA  - Am J Nephrol
JT  - American journal of nephrology
JID - 8109361
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (urate transporter)
RN  - 268B43MJ25 (Uric Acid)
RN  - PO572Z7917 (Probenecid)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors/biosynthesis
MH  - Muscle, Smooth, Vascular/*cytology/*metabolism
MH  - Myocytes, Smooth Muscle/*cytology/metabolism
MH  - Organic Anion Transporters/antagonists & inhibitors/*metabolism
MH  - Probenecid/pharmacology
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Uric Acid/*pharmacokinetics/*pharmacology
EDAT- 2005/08/23 09:00
MHDA- 2005/12/24 09:00
CRDT- 2005/08/23 09:00
PHST- 2005/04/22 00:00 [received]
PHST- 2005/07/05 00:00 [accepted]
PHST- 2005/08/23 09:00 [pubmed]
PHST- 2005/12/24 09:00 [medline]
PHST- 2005/08/23 09:00 [entrez]
AID - 87713 [pii]
AID - 10.1159/000087713 [doi]
PST - ppublish
SO  - Am J Nephrol. 2005 Sep-Oct;25(5):425-33. doi: 10.1159/000087713. Epub 2005 Aug 
      19.