PMID- 16987003
OWN - NLM
STAT- MEDLINE
DCOM- 20070104
LR  - 20180815
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 8
IP  - 9-10
DP  - 2006 Sep-Oct
TI  - Mechanoregulation of monocyte chemoattractant protein-1 expression in rat 
      vascular smooth muscle cells.
PG  - 1461-71
AB  - The authors have previously shown that arterial wall strain mediates the 
      development of vessel wall inflammation in experimental hypertension. The current 
      studies explore the mechanoregulation of monocyte chemoattractant protein-1 
      (MCP-1), a potent pro-inflammatory chemokine, by mitogen-activated protein 
      kinases (MAPK) and oxidative stress. Rat aortic smooth muscle (RASM) cells were 
      subjected to cyclic strain on a uniform biaxial strain device. Strain rapidly 
      activated both ERK1/2(MAPK) and p38(MAPK), with peak activation at 5 min. Strain 
      induced a twofold increase in MCP-1 mRNA, which was attenuated by PD 98059, a 
      specific ERK1/2(MAPK) inhibitor, and SB 203580, a specific p38(MAPK) inhibitor. 
      Cyclic strain also increased production of superoxide anion via an NADPH 
      oxidase-dependent mechanism. To assess the potential role of reactive oxygen 
      species in MAPK activation, cells were stretched in the presence of 
      N-acetylcysteine, which had no effect on p38(MAPK) activation, but significantly 
      inhibited ERK1/2(MAPK) activation and MCP-1 expression. In conclusion, 
      redox-sensitive activation of ERK1/2(MAPK) and redox-insensitive activation of 
      p38(MAPK) regulate straininduced MCP-1 expression in RASM cells. These findings 
      define a role for MAPK signal transduction in establishing a pro-inflammatory 
      state in the arterial wall, and thus implicate a potential molecular link between 
      arterial wall strain and atherosclerosis.
FAU - Guest, Thomas M
AU  - Guest TM
AD  - Division of Cardiology, Atlanta VAMC and Emory University School of Medicine, 
      Atlanta, Georgia 30322, USA.
FAU - Vlastos, George
AU  - Vlastos G
FAU - Alameddine, Fadi M F
AU  - Alameddine FM
FAU - Taylor, W Robert
AU  - Taylor WR
LA  - eng
GR  - HL-09875/HL/NHLBI NIH HHS/United States
GR  - P01 HL58000/HL/NHLBI NIH HHS/United States
GR  - R01 HL70531/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Antisense)
RN  - 11062-77-4 (Superoxides)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 1.6.3.- (NADPH Oxidase 1)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Catalase/genetics/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism
MH  - Flavonoids/pharmacology
MH  - Gene Expression/drug effects
MH  - Hydrogen Peroxide/metabolism
MH  - Imidazoles/pharmacology
MH  - Mechanotransduction, Cellular/*physiology
MH  - Muscle, Smooth, Vascular/cytology
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism
MH  - NADH, NADPH Oxidoreductases/genetics
MH  - NADPH Oxidase 1
MH  - Oxidation-Reduction
MH  - Phosphorylation
MH  - Physical Stimulation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Pyridines/pharmacology
MH  - RNA, Antisense/genetics
MH  - Rats
MH  - Superoxides/metabolism
MH  - Transfection
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
EDAT- 2006/09/22 09:00
MHDA- 2007/01/05 09:00
CRDT- 2006/09/22 09:00
PHST- 2006/09/22 09:00 [pubmed]
PHST- 2007/01/05 09:00 [medline]
PHST- 2006/09/22 09:00 [entrez]
AID - 10.1089/ars.2006.8.1461 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1461-71. doi: 
      10.1089/ars.2006.8.1461.