Abstract
Pathological left-ventricle hypertrophy is a cardiovascular disorder resulting in the thickening of the ventricle wall due to abnormal cardiomyocyte growth. The downregulation of miR-1 in hypertrophic cardiomyocytes has been identified as an early disease marker, with the delivery of miR-1 as a promising treatment strategy. Ultrasound and microbubbles offer an exciting approach to image-guided and site-specific cardiac gene delivery. The objective of this study is to show the feasibility of viable ultrasound and microbubble-mediated delivery of miR-1 in vivo. Sprague–Dawley rats were injected via tail vein with a suspension of miR-1 mimic (0.6 mg/kg) and Definity. The rats were then treated with a high MI (1.34) flash sequence for 20 min using a C5-2 probe with a Phillips iU22. Delivery was confirmed on isolated heart tissue with RT-qPCR and Western blots for miR-1 and protein expression, respectively. miR-1 delivery in healthy male rats resulted in a 1.33-fold (p = 0.05) increase in miR-1 as compared to sham controls. This resulted in a decrease in hypertrophic protein expression (1.18-fold in TWF1, p = 0.17; 1.23-fold in MEF2A, p = 0.07; 1.25-fold in CX43, p = 0.03). Our data demonstrate the feasibility of using ultrasound and microbubbles as an image-guided delivery method for molecular therapeutics in cardiovascular disorders.
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