Back to Search Start Over

Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter.

Authors :
Kang DH
Han L
Ouyang X
Kahn AM
Kanellis J
Li P
Feng L
Nakagawa T
Watanabe S
Hosoyamada M
Endou H
Lipkowitz M
Abramson R
Mu W
Johnson RJ
Source :
American journal of nephrology [Am J Nephrol] 2005 Sep-Oct; Vol. 25 (5), pp. 425-33. Date of Electronic Publication: 2005 Aug 19.
Publication Year :
2005

Abstract

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.<br />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.<br />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.<br />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.<br /> (Copyright (c) 2005 S. Karger AG, Basel.)

Details

Language :
English
ISSN :
0250-8095
Volume :
25
Issue :
5
Database :
MEDLINE
Journal :
American journal of nephrology
Publication Type :
Academic Journal
Accession number :
16113518
Full Text :
https://doi.org/10.1159/000087713