PMID- 12624005
OWN - NLM
STAT- MEDLINE
DCOM- 20030414
LR  - 20161124
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 41
IP  - 3 Pt 2
DP  - 2003 Mar
TI  - Molecular mechanisms mediating inflammation in vascular disease: special 
      reference to monocyte chemoattractant protein-1.
PG  - 834-41
AB  - There are several clinical challenges for the treatment of intractable 
      cardiovascular diseases, including restenosis, atherosclerotic complications 
      resulting from plaque rupture, severe tissue ischemia, and heart failure. 
      Emerging evidence suggests that an inflammatory process is involved in the 
      pathogenesis of such intractable diseases. In particular, inflammatory responses 
      to arterial injury, which cause continuous recruitment and activation of 
      monocytes mainly through activation of the monocyte chemoattractant protein-1 
      (MCP-1) pathway, have a central role in restenosis and atherogenesis. We recently 
      devised a new strategy for anti-MCP-1 therapy by transfecting an N-terminal 
      deletion mutant of the MCP-1 gene into skeletal muscles. This mutant MCP-1 lacks 
      the N-terminal amino acids 2 to 8, called 7ND, and works as a dominant-negative 
      inhibitor of MCP-1. We demonstrated that 7ND gene transfer suppresses monocyte 
      infiltration/activation after arterial injury and markedly inhibits experimental 
      restenosis in animals after balloon injury or stent placement. Furthermore, 7ND 
      gene transfer not only attenuated the development of early atherosclerotic 
      lesions but also limited progression of preexisting atherosclerotic lesions and 
      changed the lesion composition into a more stable phenotype in 
      hypercholesterolemic mice. Vascular inflammation mediated by MCP-1 might create a 
      positive feedback loop to enhance restenotic and atherosclerotic changes through 
      activating lesional monocytes. Therefore, vascular inflammation mediated by MCP-1 
      has a central role in the development of experimental restenosis, 
      atherosclerosis, and plaque destabilization, leading to acute coronary syndrome. 
      This strategy for gene therapy might be useful against human restenosis, thereby 
      opening a new therapeutic window for antirestenosis and antiatherosclerosis 
      paradigms.
FAU - Egashira, Kensuke
AU  - Egashira K
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. 
      egashira@cardiol.med.kyushu-u.ac.jp
LA  - eng
PT  - Journal Article
DEP - 20021230
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Animals
MH  - Arteriosclerosis/pathology/therapy
MH  - Cardiovascular Diseases/*immunology/therapy
MH  - Carotid Stenosis/diagnostic imaging/therapy
MH  - Chemokine CCL2/genetics/*physiology
MH  - Coronary Restenosis/therapy
MH  - Genetic Therapy
MH  - Haplorhini
MH  - Inflammation/etiology
MH  - Injections, Intramuscular
MH  - Mice
MH  - Models, Cardiovascular
MH  - Mutation
MH  - Plasmids/administration & dosage
MH  - Rabbits
MH  - Rats
MH  - Transfection
MH  - Ultrasonography
EDAT- 2003/03/08 04:00
MHDA- 2003/04/15 05:00
CRDT- 2003/03/08 04:00
PHST- 2003/03/08 04:00 [pubmed]
PHST- 2003/04/15 05:00 [medline]
PHST- 2003/03/08 04:00 [entrez]
AID - 01.HYP.0000051642.65283.36 [pii]
AID - 10.1161/01.HYP.0000051642.65283.36 [doi]
PST - ppublish
SO  - Hypertension. 2003 Mar;41(3 Pt 2):834-41. doi: 
      10.1161/01.HYP.0000051642.65283.36. Epub 2002 Dec 30.