GENE-THERAPY FOR VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION AFTER ARTERIAL INJURY
GENE-THERAPY FOR VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION AFTER ARTERIAL INJURY
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DOI：
10.1126/science.8047883
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发表时间：
1994-08-05
期刊：
影响因子：
56.9
通讯作者：
NABEL, EG
中科院分区：
文献类型：
--
作者：
OHNO, T;GORDON, D;NABEL, EG
血管平滑肌细胞的积累是动脉损伤的结果，是血管增生性疾病的主要特征。在这些情况下抑制平滑肌细胞增殖的分子方法可能会限制内膜扩张。通过将编码疱疹病毒胸苷激酶（tk）的腺病毒载体导入到被导管上的球囊损伤的猪动脉中，解决了这个问题。这些平滑肌细胞被证明可以被腺病毒载体感染，tk基因的引入使它们对核苷类似物更昔洛韦敏感。当这种载体被引入到猪动脉后，立即球囊损伤，内膜增生减少后，更昔洛韦治疗的过程。未观察到严重的局部或全身毒性。这些数据表明，局部催化细胞毒性药物形成的酶的瞬时表达可能会限制球囊损伤后平滑肌细胞的增殖。
Accumulation of vascular smooth muscle cells as a consequence of arterial injury is a major feature of vascular proliferative disorders. Molecular approaches to the inhibition of smooth muscle cell proliferation in these settings could potentially limit intimal expansion. This problem was approached by introducing adenoviral vectors encoding the herpesvirus thymidine kinase (tk) into porcine arteries that had been injured by a balloon on a catheter. These smooth muscle cells were shown to be infectable with adenoviral vectors, and introduction of the tk gene rendered them sensitive to the nucleoside analog ganciclovir. When this vector was introduced into porcine arteries immediately after a balloon injury, intimal hyperplasia decreased after a course of ganciclovir treatment. No major local or systemic toxicities were observed. These data suggest that transient expression of an enzyme that catalyzes the formation of a cytotoxic drug locally may limit smooth muscle cell proliferation in response to balloon injury.