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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
- 강덕희
- Issue Date
- 2003
- Journal Title
- Hypertension
- ISSN
- 0194-911X
- Citation
- Hypertension vol. 41, no. 6, pp. 1287 - 1293
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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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