Abstract 14973: Delivery Of microRna Mimics To Cardiomyocytes Using Ultrasound Responsive Microbubbles
Cardiovascular disease accounts for approximately 36% of deaths in Europe and the United States, with myocardial infarction and heart failure representing 80% of cardiovascular deaths. Heart failure is a clinical syndrome caused by ventricular remodelling due to injury to the myocardium that results in reduced cardiac output and a reduction in the heart's ability to meet functional requirements. There is no cure for this progressive condition. It is proposed that miRNA based therapeutics can be implemented to target specific genetic pathways to reduce the onset of hypertrophy and may be of significant clinical relevance in modulating the negative myocardial remodelling seen after injury. This project aims to assess the efficacy of ultrasound mediated microbubble delivery of miRNA mimics to cardiomyocytes to enhance the therapeutic potential of miRNA modifiers in heart failure. Cationic lipid microbubbles were prepared and characterized pre and post complexation with pGFP or miRNA mimics. The HL-1 cardiomyocyte cell line was transfected initially with a pGFP-lipid microbubble complex using defined ultrasound parameters. A transfection efficiency of 76.53±2.24% was achieved using this regime in comparison to 29.2±2.84% & 38.53±6.26% using liposome or commercially available FUGENE respectively. Using these parameters miRNA mimics were delivered to HL-1 cells with a transfection efficiency of 18.73±1.79%. This data demonstrates the potential of ultrasound responsive microbubble mediated delivery of miRNA mimics to cardiomyocytes. It has the potential to act as a novel delivery platform for miRNAs which may enhance the efficacy of such therapies in the future.
- © 2011 by American Heart Association, Inc.