Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium
Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium
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DOI：
10.1161/01.cir.101.22.2554
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发表时间：
2000-06-06
期刊：
影响因子：
37.8
通讯作者：
Grayburn, PA
中科院分区：
文献类型：
--
作者：
Shohet, RV;Chen, SY;Grayburn, PA
背景：无创、组织特异性地向心脏输送治疗药物将是一种有价值的临床工具。方法和结果：将含有β -半乳糖苷酶的重组腺病毒在组成型启动子的驱动下，吸附在白蛋白包被的全氟丙烷填充的微泡表面，在同时进行超声心动图或不同时进行超声心动图的情况下，将这些微泡注入大鼠颈静脉。其他对照包括不含病毒的微泡超声、单独的病毒和病毒加超声。一组接受超声介导的微泡破坏，然后进行腺病毒输注。4天后处死大鼠，检测-半乳糖苷酶的表达。超声介导破坏含病毒微泡的所有大鼠心脏均显示5-溴-4-氯-3-吲哚- β - d-半乳糖苷底物的细胞核染色，表明转基因表达。对照动物心肌均无β -半乳糖苷酶转基因表达。经定量分析，处理组β -半乳糖苷酶活性比对照组高10倍(P
Background-The noninvasive, tissue-specific delivery of therapeutic agents to the heart would be a valuable clinical tool. This study addressed the hypothesis that albumin-coated microbubbles could be used to effectively deliver an adenoviral transgene to rat myocardium by ultrasound-mediated microbubble destruction,Methods and Results-Recombinant adenovirus containing beta-galactosidase and driven by a constitutive promoter was attached to the surface of albumin-coated, perfluoropropane-filled microbubbles, These bubbles were infused into the jugular vein of rats with or without simultaneous echocardiography. Additional controls included ultrasound of microbubbles that did not contain virus, virus alone, and virus plus ultrasound. One group underwent ultrasound-mediated destruction of microbubbles followed by adenovirus infusion. Rats were killed after 4 days and examined for beta-galactosidase expression. The hearts of all rats that underwent ultrasound-mediated destruction of microbubbles containing virus showed nuclear staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside substrate, indicating expression of the transgene. None of the control animals showed myocardial expression of the beta-galactosidase transgene. By quantitative analysis, beta-galactosidase activity was 10-fold higher in the treated group than in controls (P