DATE : 16-03-13 12:01
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Local RAD 50 gene delivery induces regression of preformed porcine coronary in-stent neointimal hyperplasia.
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WRITER :
stent
 HIT : 1,322
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 B19._J_Gene_Med._2004;6_1_93-104..pdf (354.9K) [0] DATE : 2016-03-13 12:01:09 |
B19. Ahn YK, Kook H, Jeong MH, Cho JG, Park JC, Kang JC, Kim KK; J Gene Med. 2004;6(1)93-104.
(Abstract)
BACKGROUND:
Recently, we observed that overexpression of human RAD50 (hRAD50) induced p21-dependent cytotoxicity in various cultured cells, and rat and mouse tumor models. This study investigated the characteristics of endothelial cell (EC) death by hRAD50 and the potential utility of hRAD50 in the development of gene therapies for vascular restenosis.
METHODS:
We studied the effects of transient hRAD50 gene transfer using nonliposomal lipid on the survival of primary cultured human coronary arterial EC and smooth muscle cells (SMC). Palmaz-Schatz stents were deployed in two epicardial coronary arteries in each pig (n = 10). Two weeks later, the patency of the stented arteries was documented by coronary angiography, and the hRAD50 construct or empty vector mixed with lipid was delivered to one of the stented arteries in each pig using a Dispatch catheter. Coronary angiography was repeated 2 weeks after gene delivery and histological examination was performed.
RESULTS:
Lipid-mediated hRAD50 gene transfer resulted in the death of EC and SMC. It also increased endothelial nitric oxide synthase (eNOS) expression and nitrite production as well as p21 expression. Pretreatment with NOS and pan-caspase inhibitors completely prevented EC death by hRAD50. In the hRAD50-delivered arteries, the percentage of diameter stenosis, neointimal area, and pathologic area of stenosis were significantly smaller than in the control arteries. eNOS expression increased in the hRAD50-delivered arteries. Systemic hematologic and chemical values were not affected by gene delivery.
CONCLUSIONS:
Significant regression of preformed in-stent neointimal hyperplasia was induced by local hRAD50 gene delivery to stented porcine coronary arteries without apparent systemic toxicity.
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