Ultrasound-mediated microbubble destruction enhances VEGF gene delivery to the infarcted myocardium in rats

Objective: To investigate the possibility of improving the delivery of vascular endothelial growth factor (VEGF) gene to the myocardium in rats by using ultrasound-mediated microbubble destruction (UMMD). Methods: Fifteen male Wistar rats underwent left anterior descending coronary artery ligation in this study. The rats were divided into three groups 3 days after ligation. Ultrasound microbubble vectors (UMVs) attaching to pcD2VEGF121 gene were injected into the tail vein of rats with or without simultaneous echocardiographic microbubble destruction in two groups. The third group was used as control group. VEGF protein expression and formation of new blood vessels were evaluated by immunohistochemical technique during autopsy on 15 rats at 2 weeks after gene transformation. Microvascular density (MVD) in the area with myocardial infarction was counted under a microscope. Results: VEGF protein expression and MVD in the ischemic myocardium were higher in the rats receiving UMMD than in the group that did not receive UMMD. Conclusion: UMMD is a noninvasive method to effectively improve the delivery of targeted genes to the heart. (C) 2004 Elsevier Inc. All rights reserved.