Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation
Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation
复制标题
DOI：
10.1038/5538
复制
发表时间：
1999-02-01
期刊：
影响因子：
82.9
通讯作者：
Rabinovitch, M
中科院分区：
文献类型：
--
作者：
Mason, CAE;Bigras, JL;Rabinovitch, M
动脉导管的闭合需要在出生前形成内膜垫，其在出生时闭塞血管腔。然而，患有严重先天性心脏病的新生儿的存活取决于导管的通畅性。我们采用基因转移的方法，通过靶向内膜垫形成所需的纤维连接蛋白依赖性平滑肌细胞迁移来建立动脉导管未闭。胎羊动脉导管在子宫内转染血凝病毒的日本脂质体含有质粒编码的'诱饵' RNA螯合纤连蛋白mRNA结合蛋白。纤连蛋白翻译被抑制，内膜垫形成被阻止。因此，我们建立了必要的作用，纤维连接蛋白依赖性平滑肌细胞迁移的内膜垫形成在完整的动物和可行性，将生物工程在先天性心脏病的管理。
Closure of the ductus arteriosus requires prenatal formation of intimal cushions, which occlude the vessel lumen at birth. Survival of newborns with severe congenital heart defects, however, depends on ductal patency. We used a gene transfer approach to create a patent ductus arteriosus by targeting the fibronectin-dependent smooth muscle cell migration required for intimal cushion formation. Fetal lamb ductus arteriosus was transfected in utero with hemagglutinating virus of Japan liposomes containing plasmid encoding 'decoy' RNA to sequester the fibronectin mRNA binding protein. Fibronectin translation was inhibited and intimal cushion formation was prevented. We thus established the essential role of fibronectin-dependent smooth muscle cell migration in intimal cushion formation in the intact animal and the feasibility of incorporating biological engineering in the management of congenital heart disease.