PMID- 9264504
OWN - NLM
STAT- MEDLINE
DCOM- 19970915
LR  - 20220222
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 96
IP  - 3
DP  - 1997 Aug 5
TI  - Nitric oxide regulates monocyte chemotactic protein-1.
PG  - 934-40
AB  - BACKGROUND: Monocyte chemotactic protein-1 (MCP-1) is a 76-amino-acid chemokine 
      thought to be the major chemotactic factor for monocytes. We and others have 
      demonstrated that NO inhibits monocyte-endothelial cell interactions and 
      atherogenesis. We hypothesize that the antiatherogenic effect of NO may be due in 
      part to its inhibition of MCP-1 expression. METHODS AND RESULTS: Smooth muscle 
      cells (SMCs) were isolated from normal rabbit aortas by the explant method. Cells 
      were then exposed to LPS (10 microg/mL), native LDL, or oxidized LDL (30 
      microg/mL) for 6 hours. The expression of MCP-1 in SMCs and chemotactic activity 
      in the conditioned medium were induced by lipopolysaccharide (LPS) or by oxidized 
      LDL but not native LDL. The induction of MCP-1 by cytokines or oxidized 
      lipoproteins was associated with an increased generation of superoxide anion by 
      the SMCs and increased activity of the transcriptional protein nuclear 
      factor-kappaB (NFkappaB). The induced expression of MCP-1 and activation of 
      NFkappaB were reduced by previous exposure of the SMCs to the NO donor 
      DETA-NONOate (100 micromol/L) (P<.05). To determine whether NO exerted its effect 
      at a transcriptional level, SMCs and COS cells were transfected with a 400-bp 
      fragment of the MCP-1 promoter. Promoter activity was enhanced by oxidized LDL, 
      and LPS was inhibited by DETA-NO. Nuclear run-on assays confirmed that the effect 
      of NO occurred at a transcriptional level. To investigate the role of endogenous 
      NO in the regulation of MCP-1 in vivo, New Zealand White rabbits were fed normal 
      chow, normal chow plus nitro-L-arginine (LNA), high-cholesterol diet (Chol), or 
      high-cholesterol diet supplemented with L-arginine (Arg). After 2 weeks, thoracic 
      aortas were harvested and total RNA was isolated. Northern analysis using 
      full-length MCP-1 cDNA demonstrated increased expression in Chol and LNA aortas; 
      this expression was decreased in aortas from Arg animals. CONCLUSIONS: These 
      studies indicate that the antiatherogenic effect of NO may be mediated in part by 
      its inhibition of MCP-1 expression.
FAU - Tsao, P S
AU  - Tsao PS
AD  - Division of Cardiovascular Medicine, Stanford University School of Medicine, 
      Calif 94305-5246, USA.
FAU - Wang, B
AU  - Wang B
FAU - Buitrago, R
AU  - Buitrago R
FAU - Shyy, J Y
AU  - Shyy JY
FAU - Cooke, J P
AU  - Cooke JP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Triazenes)
RN  - 11062-77-4 (Superoxides)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Chemokine CCL2/antagonists & inhibitors/*metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Muscle, Smooth, Vascular/cytology/metabolism
MH  - Nitric Oxide/*physiology
MH  - Rabbits
MH  - Superoxides/metabolism
MH  - Triazenes/pharmacology
EDAT- 1997/08/05 00:00
MHDA- 1997/08/05 00:01
CRDT- 1997/08/05 00:00
PHST- 1997/08/05 00:00 [pubmed]
PHST- 1997/08/05 00:01 [medline]
PHST- 1997/08/05 00:00 [entrez]
AID - 10.1161/01.cir.96.3.934 [doi]
PST - ppublish
SO  - Circulation. 1997 Aug 5;96(3):934-40. doi: 10.1161/01.cir.96.3.934.