[Adenovirus-mediated transfer of TIMP-4 gene inhibits neointimal formation after balloon injury].
OBJECTIVE
To investigate the effects of human tissue inhibitor of matelloproteinase-4 (TIMP-4) on vascular smooth muscle cells (VSMCs) migration and the neointimal formation after balloon injury in rats.


METHODS
The cultured VSMCs were transfected with an adenoviral vector containing human TIMP-4 gene, AdTIMP-4. Effect of TIMP-4 on VSMC migration was investigated by monolayer cell scrape. AdTIMP-4, control adenoviral vector or PBS was transduced into the rat carotid artery from the adventitial after carotid artery injury. Cell number within the internal elastic lamina 4 days after gene transfer was counted and neointima/media area ratio 28 days after gene transfer was calculated.


RESULTS
The migration distance of VSMCs infected with AdTIMP-4 was inhibited markedly. Morphometric analysis demonstrated a statistically significant reduction in the number of cells migrated into neointima compared with controls [(32.5 +/- 4.8) cells per section, (33.8 +/- 7.0) cells per section and (8.2 +/- 2.4) cells per section for uninfected, AdGFP-treated and AdTIMP-4-treated arteries, respectively]. There was a reduction of intima/media ratio of TIMP-4-treated group by 66.5% compared with control groups 28 days after gene transfer (P < 0.01). There was no statistical difference between the control adenoviral vector group and PBS group.


CONCLUSIONS
Adenoviral mediated gene transfer of TIMP-4 inhibits migration of VSMC and significantly reduces neointimal hyperplasia in the rat carotid balloon injury model. The TIMP-4 gene transfer is a potential therapeutic approach to preventing neointimal formation after balloon injury.
Guo
Yanhong
Y
Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
Li
Qian
Q
Chen
Guanghui
G
Tang
Jian
J
Gao
Wei
W
D000256:Adenoviridae; D000818:Animals; D002339:Carotid Arteries; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular; D005822:Genetic Vectors; D006801:Humans; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle; D058426:Neointima / Q000517:prevention & control*; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*; D014162:Transfection; D017539:Tunica Intima; D017540:Tunica Media; D000097792:Tissue Inhibitor of Metalloproteinase-4
D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4