PMID- 11056100
OWN - NLM
STAT- MEDLINE
DCOM- 20001121
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 102
IP  - 18
DP  - 2000 Oct 31
TI  - Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced 
      by chronic blockade of nitric oxide synthesis.
PG  - 2243-8
AB  - BACKGROUND: Chronic inhibition of endothelial nitric oxide (NO) synthesis by the 
      administration of N:(omega)-nitro-L-arginine methyl ester (L-NAME) to rats 
      induces early vascular inflammatory changes (monocyte infiltration into coronary 
      vessels and monocyte chemoattractant protein-1 [MCP-1] expression) as well as 
      subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and 
      cardiac fibrosis. However, the role of MCP-1 in this process is not known. 
      METHODS AND RESULTS: We investigated the effect of a specific monoclonal 
      anti-MCP-1 neutralizing antibody in rats treated with L-NAME to determine the 
      role of monocytes in the regulation of cardiovascular remodeling. We found 
      increased expression of MCP-1 mRNA in vascular endothelial cells and monocytes in 
      inflammatory lesions. Cotreatment with an anti-MCP-1 antibody, but not with 
      control IgG, prevented the L-NAME-induced early inflammation and reduced late 
      coronary vascular medial thickening. In contrast, the anti-MCP-1 antibody did not 
      decrease the development of perivascular fibrosis, the expression of transforming 
      growth factor (TGF)-beta(1) mRNA, or systolic pressure overload induced by L-NAME 
      administration. CONCLUSIONS: These results suggest that MCP-1 is necessary for 
      the development of medial thickening as well as monocyte recruitment. In 
      contrast, the pathogenesis of fibrosis may involve other factors, such as 
      TGF-beta(1).
FAU - Koyanagi, M
AU  - Koyanagi M
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Egashira, K
AU  - Egashira K
FAU - Kitamoto, S
AU  - Kitamoto S
FAU - Ni, W
AU  - Ni W
FAU - Shimokawa, H
AU  - Shimokawa H
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  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 9007-34-5 (Collagen)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Blood Pressure/drug effects
MH  - Cell Division/drug effects
MH  - Chemokine CCL2/antagonists & inhibitors/*metabolism/pharmacology
MH  - Chronic Disease
MH  - Collagen/biosynthesis/genetics
MH  - Coronary Artery Disease/chemically induced/*metabolism/pathology
MH  - Dermis/drug effects/pathology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Fibrosis/pathology
MH  - Inflammation/chemically induced/pathology
MH  - Male
MH  - Monocytes/cytology/drug effects
MH  - Myocardium/metabolism
MH  - NG-Nitroarginine Methyl Ester
MH  - Nitric Oxide Synthase/*antagonists & inhibitors/metabolism
MH  - Peptidyl-Dipeptidase A/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Recombinant Proteins/antagonists & inhibitors/metabolism/pharmacology
MH  - Transforming Growth Factor beta/biosynthesis/genetics
MH  - Transforming Growth Factor beta1
MH  - Ventricular Remodeling
EDAT- 2000/11/01 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/01 11:00
PHST- 2000/11/01 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/01 11:00 [entrez]
AID - 10.1161/01.cir.102.18.2243 [doi]
PST - ppublish
SO  - Circulation. 2000 Oct 31;102(18):2243-8. doi: 10.1161/01.cir.102.18.2243.