Phillips Linsey C, Klibanov Alexander L, Bowles Douglas K, Ragosta Michael, Hossack John A, Wamhoff Brian R
Biomedical Engineering, Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
J Vasc Res. 2010;47(3):270-4. doi: 10.1159/000258905. Epub 2009 Nov 18.
Safety concerns associated with drug-eluting stents have spurred interest in alternative vessel therapeutics following angioplasty. Microbubble contrast agents have been shown to increase gene transfection in vivo in the presence of ultrasound.
OBJECTIVES/METHODS: The purpose of this study was to determine whether an intravascular ultrasound (IVUS) catheter could mediate plasmid DNA transfection from microbubble carriers to the porcine coronary artery wall following balloon angioplasty.
In the presence of plasmid-coupled microbubbles in vitro only cells exposed to ultrasound from the modified IVUS catheter significantly expressed the transgene. A porcine left anterior descending coronary artery underwent balloon angioplasty followed by injection and insonation of microbubbles from the IVUS catheter at the site of angioplasty. After 3 days, an approximately 6.5-fold increase in transgene expression was observed in arteries that received microbubbles and IVUS compared to those that received microbubbles with no IVUS.
The results of this study demonstrate for the first time that IVUS is required to enhance gene transfection from microbubble carriers to the vessel wall in vivo. This technology may be applied to both drug and gene therapy to reduce vessel restenosis.
与药物洗脱支架相关的安全问题激发了人们对血管成形术后替代性血管治疗方法的兴趣。已证明微泡造影剂在超声存在的情况下可增加体内基因转染。
目的/方法：本研究的目的是确定血管内超声（IVUS）导管在球囊血管成形术后能否介导质粒DNA从微泡载体转染至猪冠状动脉壁。
在体外存在质粒偶联微泡的情况下，只有暴露于改良IVUS导管超声的细胞显著表达转基因。对猪左前降支冠状动脉进行球囊血管成形术，然后在血管成形部位从IVUS导管注射并照射微泡。3天后，与未接受IVUS的微泡组相比，接受微泡和IVUS的动脉中转基因表达增加了约6.5倍。
本研究结果首次证明，在体内需要IVUS来增强基因从微泡载体向血管壁的转染。该技术可应用于药物和基因治疗以减少血管再狭窄。
