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Bcl-2 gene transfer using ultrasound targetted microbubble destruction into infarcted rat myocardium.
광주기독병원¹ , 전남대학교 병원 심장센터²
이승욱¹, 안영근², 김용숙², 권진숙², 박혜정², 홍문화², 강동구¹, 김계훈², 정명호², 조정관², 조상기¹, 박종춘²
Background: Gene therapy has emerged as a genuine therapeutic option with the potential to alter the manner in which cardiologists manage the two most common cardiac disorders afflicting adult coronary artery disease and congestive heart failure. Ultrasound contrast agents have been used in diagnostic echocardiography for several decades. In recent years, several investigators have used ultrasound contrast agents as a tool for organ-specific drug and gene delivery. In addition, recent study showed that transgenic expression of Bcl-2 using viral vector reduces ischemia and reperfusion injury in myocardial ischemia. Ultrasound-targeted microbubble destruction (UTMD) has been proposed as a new technique for site-specific gene delivery and Bcl-2 gene transfer using UTMD to rat myocardium was attempted in this study. Methods and Results: Sprague-Dawley rats received treatment: microbubbles loaded with plasmids endocing the bcl-2 gene, or microbubbles alone via jugular vein. During the infusion, ultrasound was directed to the heart using a commercially available ultrasound transducer. Four bursts of ultrasound were triggered to every fourth end-systole. Two groups of Group 1: myocardial infarct with UTMD loaded with plasmids encoding the human Bcl-2 gene treatment (0.6 mg DNA/kg) in left ventricular cavity (n=10) Group 2: myocardial infarct group with the same treatment without Bcl-2 gene plasmid in left ventricular cavity (n=10) were compared. After UTMD, rats were sacrificed at day 7, 14. The heart was harvested for histology and assessment of bcl-2 protein by Western blot, mRNA by RT-PCR and immunohistochemisty using autoantibody of bcl-2 gene. And functional study in the rat infarct model with gene delivery of Bcl-2 using UTMD will be performed. The precise results will be presented at autumn conference. Conclusion: Myocardial gene therapy using UTMD has a possibility to be a novel method in treatment of ischemic heart failure.


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