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Cited by 786

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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

Kanellis, John, Watanabe, Susumu, Li, Jin H., Kang, Duk Hee, Li, Ping, Nakagawa, Takahiko, Wamsley, Ann, Sheikh-Hamad, David, Lan, Hui Y., Feng, Lili, Johnson, Richard J.·2003·Hypertension

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.

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Crossref · 10.1161/01.hyp.0000072820.07472.3b

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Metadata

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.
Venue
Hypertension
Published
2003-06
Volume
41
Issue
6
Pages
1287-1293
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
OpenAlex
W2151834039
Cited by
786
References
2
FWCI
13.70
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2. https://app.cochat.ai/papers/10.1161/01.hyp.0000072820.07472.3b
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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. (2003). Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2. Hypertension. https://doi.org/10.1161/01.hyp.0000072820.07472.3b

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