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Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2

Title
Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2
Authors
Kanellis J.Watanabe S.Li J.H.Kang D.H.Li P.Nakagawa T.Wamsley A.Sheikh-Hamad D.Lan H.Y.Feng L.Johnson R.J.
Ewha Authors
강덕희
SCOPUS Author ID
강덕희scopus
Issue Date
2003
Journal Title
Hypertension
ISSN
0194-911XJCR Link
Citation
vol. 41, no. 6, pp. 1287 - 1293
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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-κB 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.
DOI
10.1161/01.HYP.0000072820.07472.3B
Appears in Collections:
의과대학 > 의학과 > Journal papers
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