Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro

Background-Restenosis after percutaneous coronary intervention remains a se rious clinical problem. Progress in local gene therapy to prevent restenosi s has been hindered by concerns over the safety and efficacy of viral vecto rs and the limited efficiency of nonviral techniques, This study investigat es the use of adjunctive ultrasound to enhance nonviral gene delivery. Methods and Results-Cultured porcine vascular smooth muscle cells (VSMCs) a nd endothelial cells (ECs) were transfected with naked or liposome-complexe d luciferase reporter plasmid for 3 hours. Ultrasound exposure (USE) for 60 seconds at 1 MHz, 0.4 W/cm(2), 30 minutes into this transfection period en hanced luciferase activity 48 hours later by 7.5-fold and 2.4-fold, respect ively, Luciferase activity after lipofection of ECs was similarly enhanced 3.3-fold by adjunctive USE. USE had no effect on cell viability, although i t inhibited VSMC but not EC proliferation. Conclusions-Adjunctive USE was associated with enhanced transgene expressio n in VSMCs and ECs and reduced VSMC but not EC proliferation in vitro, whic h suggests that ultrasound-assisted local gene therapy has potential as an antirestenotic therapy.