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

160 Citations (Scopus)

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 - 2001 Jan 1
Externally publishedYes

Keywords

  • Angiotensin II
  • Kinase
  • Muscle, smooth, vascular
  • Peptides
  • Receptors, angiotensin

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    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, 38(1), 100-104. https://doi.org/10.1161/01.HYP.38.1.100