PMID- 14739159
OWN - NLM
STAT- MEDLINE
DCOM- 20040621
LR  - 20161124
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 94
IP  - 5
DP  - 2004 Mar 19
TI  - Calcineurin promotes the expression of monocyte chemoattractant protein-1 in 
      vascular myocytes and mediates vascular inflammation.
PG  - 693-700
AB  - Although the role of the calcineurin-dependent pathway in the development of 
      cardiac hypertrophy has been intensively studied, little is known of its role in 
      vascular inflammatory diseases such as atherosclerosis and restenosis after 
      angioplasty. To help elucidate the role of calcineurin in vascular inflammation, 
      we infected cultured vascular smooth muscle cells (VSMCs) with an adenovirus 
      construct expressing a constitutively active mutant of calcineurin, and examined 
      its effect on the expression of monocyte chemoattractant protein-1 (MCP-1). We 
      also examined the role of calcineurin in vivo using a transluminal wire injury 
      model of the rat femoral artery. Forced activation of calcineurin significantly 
      increased the expression of MCP-1 both at the transcriptional and protein levels. 
      Angiotensin II (Ang II) also significantly stimulated MCP-1 expression, and this 
      increase was significantly inhibited by cyclosporin A (CyA). Constitutive 
      activation of calcineurin stabilized MCP-1 mRNA without enhancing MCP-1 promoter 
      activity. In accordance with the results, Ang II-induced increase of MCP-1 
      promoter activity was not suppressed by CyA. Ang II stabilized MCP-1 mRNA, and 
      this effect of Ang II was diminished by CyA. CyA suppressed MCP-1 expression in 
      the femoral artery after the transluminal mechanical injury. CyA also inhibited 
      macrophage infiltration and neointimal formation in the wire-injured femoral 
      arteries. These results suggested that calcineurin mediates vascular inflammation 
      via stimulation of MCP-1 expression in VSMCs and macrophage infiltration.
FAU - Satonaka, Hiroshi
AU  - Satonaka H
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
FAU - Suzuki, Etsu
AU  - Suzuki E
FAU - Nishimatsu, Hiroaki
AU  - Nishimatsu H
FAU - Oba, Shigeyoshi
AU  - Oba S
FAU - Takeda, Ryo
AU  - Takeda R
FAU - Goto, Atsuo
AU  - Goto A
FAU - Omata, Masao
AU  - Omata M
FAU - Fujita, Toshiro
AU  - Fujita T
FAU - Nagai, Ryozo
AU  - Nagai R
FAU - Hirata, Yasunobu
AU  - Hirata Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040122
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (CCL2 protein, human)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Imidazoles)
RN  - 0 (Proteins)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tetrazoles)
RN  - 11128-99-7 (Angiotensin II)
RN  - 80M03YXJ7I (Valsartan)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 6)
RN  - EC 2.7.12.2 (MAP2K6 protein, human)
RN  - EC 3.1.3.16 (Calcineurin)
RN  - HG18B9YRS7 (Valine)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Angiotensin II/antagonists & inhibitors/pharmacology
MH  - Animals
MH  - Calcineurin/chemistry/genetics/*physiology
MH  - Calcium Signaling
MH  - Calcium-Calmodulin-Dependent Protein Kinases/genetics/physiology
MH  - Cardiomyopathy, Hypertrophic/physiopathology
MH  - Cells, Cultured/drug effects/metabolism
MH  - *Chemokine CCL2
MH  - Cyclosporine/pharmacology
MH  - Femoral Artery/drug effects/injuries/metabolism/pathology
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Humans
MH  - Hyperplasia
MH  - Imidazoles/pharmacology
MH  - MAP Kinase Kinase 6
MH  - Macrophages/physiology
MH  - Muscle, Smooth, Vascular/*metabolism
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism
MH  - Promoter Regions, Genetic
MH  - *Protein Biosynthesis
MH  - Proteins/genetics
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Recombinant Fusion Proteins/physiology
MH  - Signal Transduction
MH  - Tetrazoles/pharmacology
MH  - Transcription, Genetic/drug effects
MH  - Tunica Intima/pathology
MH  - Valine/analogs & derivatives/pharmacology
MH  - Valsartan
MH  - Vasculitis/etiology/pathology/*physiopathology
EDAT- 2004/01/24 05:00
MHDA- 2004/06/23 05:00
CRDT- 2004/01/24 05:00
PHST- 2004/01/24 05:00 [pubmed]
PHST- 2004/06/23 05:00 [medline]
PHST- 2004/01/24 05:00 [entrez]
AID - 01.RES.0000118250.67032.5E [pii]
AID - 10.1161/01.RES.0000118250.67032.5E [doi]
PST - ppublish
SO  - Circ Res. 2004 Mar 19;94(5):693-700. doi: 10.1161/01.RES.0000118250.67032.5E. 
      Epub 2004 Jan 22.