학술대회안내사전등록초록등록안내초록등록/관리숙박 및 교통
초록심사

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Effects of β-catenin Gene Transfer on Survival and Apoptosis of Rat Cardiomyocytes/Fibroblasts and Left Ventricular Function and Angiogenesis in a Rat Myocardial Infarction Model
서울대학교의과대학 내과학교실; 서울대학교병원 임상의학연구소 심혈관연구실; 서울대학교병원 심혈관센터¹ :경희대학교의과대학 내과학교실²:분당서울대병원 심혈관센터³
한주용¹, 조현주¹ ,정중화¹ ,배장환² ,김태연¹ ,전수인¹ ,강현재¹ ,연태진³ ,최동주³ ,김효수¹ ,손대원¹ ,오병희¹ ,이명묵¹ ,박영배¹ ,최윤식¹
PURPOSE: β-catenin is a transcriptional regulator of several genes involved in survival and proliferation. In this study, we examined the effects of β-catenin gene transfer on survival and apoptosis of rat cardiomyocytes and fibroblasts, and investigated its effects on left ventricular (LV) function and remodeling in a rat myocardial infarction (MI) model. METHODS: In vitro, the effects of β-catenin gene transfer were examined on cardiomyocytes and fibroblasts collected from neonatal rat hearts and cultured separately. Cells transfected with either Adeno-β-catenin (Ad-catenin) or Adeno-GFP (Ad-GFP) were exposed to both proliferative and apoptotic culture conditions. In vivo, 12-week old rats were subjected to 45 minutes of coronary ligation followed by reperfusion, and were injected with either Ad-catenin (n=29) or Ad-GFP (n=29) in the MI borderzone area. Functional analysis using echocardiography was performed at 1 and 2 weeks, and histological analysis at 2 weeks after the procedure. RESULTS: In vitro, Ad-catenin reduced serum deprivation apoptosis of both cardiomyocytes and fibroblasts and augmented proliferation of fibroblasts. In addition, immunoblotting of the cell culture media showed increased VEGF expression in the Ad-catenin group compared with the Ad-GFP group. In vivo, echocardiography at 1 and 2 weeks after MI showed better preservation of anterior regional wall motion and greater ejection fraction (EF) in the Ad-catenin group compared to the Ad-GFP group (EF at 1 week: 63.5±11.5 vs 52.7±9.5 %, p<0.05, at 2 weeks: 58.5±10.7 vs 46.7±8.7 %, p<0.05). Furthermore, we observed better preservation of anterior wall thickness in the Ad-catenin group. Accordingly, on histological analysis, MI border zone thickness was greater in the Ad-catenin group (1.10±0.12 vs 0.78±0.09 mm, p<0.05 at 2 weeks). More capillaries and VEGF expression were observed in the Ad-catenin group than the Ad-GFP group. CONCLUSION: Adenovirus mediated β-catenin gene transfer in a rat MI model attenuated LV dysfunction, reduced ventricular remodeling, and enhanced capillary formation. β-catenin may play an important role in the post-MI healing process by anti-apoptotic, pro-proliferative, and angiogenic action.


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