Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells

Yuko Funakoshi, Toshihiro Ichiki, Hiroaki Shimokawa, Kensuke Egashira, Kotaro Takeda, Kozo Kaibuchi, Motohiro Takeya, Teizo Yoshimura, Akira Takeshita

Research output: Contribution to journalArticle

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Abstract

Recently, it was shown that Rho-kinase plays an important role in blood pressure regulation. However, it is not known whether Rho-kinase is involved in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine that regulates monocyte recruitment and atherogenesis. Therefore, we examined the role of Rho and Rho-kinase in the angiotensin (Ang) II-induced expression of MCP-1. Ang II dose-and time-dependently enhanced the expression of MCP-1 mRNA and the protein production in vascular smooth muscle cells. CV11974, an Ang II type 1 receptor (AT1-R) specific antagonist inhibited the enhancement of MCP-1 expression by Ang II, suggesting that the effect of Ang II is mediated by the AT1-R. Botulinum C3 exotoxin, a specific inhibitor of Rho, suppressed Ang II-induced MCP-1 production. To examine the role of Rho-kinase in Ang II-induced MCP-1 expression, we used adenovirus-mediated overexpression of the dominant negative mutant of Rho-kinase (AdDNRhoK) or Y-27632, a specific inhibitor of Rho-kinase. Both AdDNRhoK and Y-27632 strongly inhibited Ang II-induced MCP-1 expression. Although inhibition of extracellular signal-regulated protein kinase (ERK) by PD 098,059 also inhibited Ang II-induced MCP-1 expression, Y-27632 did not affect Ang II-induced activation of ERK. These results indicate that Rho-kinase plays a critical role in Ang II-induced MCP-1 production independent of ERK. The Rho-Rho-kinase pathway may be a novel target for the inhibition of Ang II signaling and the treatment of atherosclerosis.

Original languageEnglish
Pages (from-to)100-104
Number of pages5
JournalHypertension
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

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rho-Associated Kinases
Chemokine CCL2
Vascular Smooth Muscle
Angiotensin II
Smooth Muscle Myocytes
Atherosclerosis
Adenoviridae
Angiotensin II Type 1 Receptor Blockers
Exotoxins
Extracellular Signal-Regulated MAP Kinases
Chemokines
Protein Kinases
Monocytes

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells. / Funakoshi, Yuko; Ichiki, Toshihiro; Shimokawa, Hiroaki; Egashira, Kensuke; Takeda, Kotaro; Kaibuchi, Kozo; Takeya, Motohiro; Yoshimura, Teizo; Takeshita, Akira.

In: Hypertension, Vol. 38, No. 1, 01.01.2001, p. 100-104.

Research output: Contribution to journalArticle

Funakoshi, Y, Ichiki, T, Shimokawa, H, Egashira, K, Takeda, K, Kaibuchi, K, Takeya, M, Yoshimura, T & Takeshita, A 2001, 'Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells', Hypertension, vol. 38, no. 1, pp. 100-104. https://doi.org/10.1161/01.HYP.38.1.100
Funakoshi, Yuko ; Ichiki, Toshihiro ; Shimokawa, Hiroaki ; Egashira, Kensuke ; Takeda, Kotaro ; Kaibuchi, Kozo ; Takeya, Motohiro ; Yoshimura, Teizo ; Takeshita, Akira. / Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells. In: Hypertension. 2001 ; Vol. 38, No. 1. pp. 100-104.
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