PMID- 22023473
OWN - NLM
STAT- MEDLINE
DCOM- 20120820
LR  - 20191112
IS  - 1875-5631 (Electronic)
IS  - 1566-5232 (Linking)
VI  - 11
IP  - 6
DP  - 2011 Dec
TI  - Anti-inflammatory gene therapy for cardiovascular disease.
PG  - 442-6
AB  - Inflammation in the vascular wall is an essential hallmark during the development 
      of atherosclerosis, for which major leukocytes infiltrated in the lesions are 
      monocytes/macrophages. Therefore, monocyte chemoattractant protein-1 (MCP-1) and 
      its primary receptor CC chemokine receptor 2 (CCR2) are feasible molecular 
      targets for gene therapy to inhibit monocyte/macrophage-mediated inflammation in 
      atherogenesis. A mutant MCP-1 that lacks N-terminal 7 amino acids (7ND) has been 
      shown to heterodimerize with native MCP-1, bind to CCR2 and block MCP-1-mediated 
      monocyte chemotaxis by a dominant-negative manner. Gene therapy using 
      intramuscular transfection with plasmid DNA encoding 7ND showed inhibitory 
      effects on atherosclerosis in hypercholesterolemic mice, and neointima formation 
      after vascular injury in animal models. Bare metal stents for coronary 
      intervention were coated with multiple thin layers of biocompatible polymer with 
      7ND plasmid. The 7ND gene-eluting stent inhibited macrophage infiltration 
      surrounding stent struts and in-stent neointima formation in rabbit femoral 
      arteries and cynomolgus monkey iliac arteries. Finally, the authors describe new 
      application of 7ND plasmid encapsulated in polymer nanoparticle (NP) that 
      functions as gene delivery system with unique in vivo kinetics. NP-mediated 7ND 
      gene delivery inhibited MCP-1-induced chemotaxis of mouse peritoneal macrophage 
      ex vivo, which may be applicable for the treatment of atherosclerotic 
      cardiovascular disease. In conclusion, anti-inflammatory gene therapy targeting 
      MCP-1/CCR2 signal, with a novel NP-mediated gene delivery system, is a potent 
      therapeutic strategy for the treatment of cardiovascular diseases.
FAU - Matoba, Tetsuya
AU  - Matoba T
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate, School of 
      Medical Sciences, Fukuoka, Japan.
FAU - Egashira, Kensuke
AU  - Egashira K
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Gene Ther
JT  - Current gene therapy
JID - 101125446
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
SB  - IM
MH  - Animals
MH  - Arteriosclerosis/genetics
MH  - Atherosclerosis/genetics/therapy
MH  - Cardiovascular Diseases/genetics/*therapy
MH  - Chemokine CCL2/*genetics
MH  - *Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Humans
MH  - Inflammation/*genetics/therapy
MH  - Mice
MH  - Neointima/genetics
MH  - Rabbits
MH  - Receptors, CCR2/genetics
MH  - Stents
EDAT- 2011/10/26 06:00
MHDA- 2012/08/21 06:00
CRDT- 2011/10/26 06:00
PHST- 2011/05/31 00:00 [received]
PHST- 2011/06/22 00:00 [revised]
PHST- 2011/06/22 00:00 [accepted]
PHST- 2011/10/26 06:00 [entrez]
PHST- 2011/10/26 06:00 [pubmed]
PHST- 2012/08/21 06:00 [medline]
AID - BSP/CGT/E-Pub/00094 [pii]
AID - 10.2174/156652311798192888 [doi]
PST - ppublish
SO  - Curr Gene Ther. 2011 Dec;11(6):442-6. doi: 10.2174/156652311798192888.