PMID- 11463768
OWN - NLM
STAT- MEDLINE
DCOM- 20010809
LR  - 20211203
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 38
IP  - 1
DP  - 2001 Jul
TI  - Rho-kinase mediates angiotensin II-induced monocyte chemoattractant protein-1 
      expression in rat vascular smooth muscle cells.
PG  - 100-4
AB  - 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 (AT(1)-R) specific antagonist inhibited the enhancement 
      of MCP-1 expression by Ang II, suggesting that the effect of Ang II is mediated 
      by the AT(1)-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.
FAU - Funakoshi, Y
AU  - Funakoshi Y
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan.
FAU - Ichiki, T
AU  - Ichiki T
FAU - Shimokawa, H
AU  - Shimokawa H
FAU - Egashira, K
AU  - Egashira K
FAU - Takeda, K
AU  - Takeda K
FAU - Kaibuchi, K
AU  - Kaibuchi K
FAU - Takeya, M
AU  - Takeya M
FAU - Yoshimura, T
AU  - Yoshimura T
FAU - Takeshita, A
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Amides)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 11128-99-7 (Angiotensin II)
RN  - 138381-45-0 (Y 27632)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Amides/pharmacology
MH  - Angiotensin II/*pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Enzyme Activation/drug effects
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Muscle, Smooth, Vascular/*drug effects/enzymology/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/biosynthesis/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - rho-Associated Kinases
MH  - rhoA GTP-Binding Protein
EDAT- 2001/07/21 10:00
MHDA- 2001/08/10 10:01
CRDT- 2001/07/21 10:00
PHST- 2001/07/21 10:00 [pubmed]
PHST- 2001/08/10 10:01 [medline]
PHST- 2001/07/21 10:00 [entrez]
AID - 10.1161/01.hyp.38.1.100 [doi]
PST - ppublish
SO  - Hypertension. 2001 Jul;38(1):100-4. doi: 10.1161/01.hyp.38.1.100.