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(Circulation. 1999;99:2617-2620.)
© 1999 American Heart Association, Inc.

Brief Rapid Communications

Ultrasound Enhances Reporter Gene Expression After Transfection of Vascular Cells In Vitro

Allan Lawrie, BSc; Axel F. Brisken, PhD; Sheila E. Francis, PhD; David I. Tayler, BM, BSc; Janet Chamberlain, PhD; David C. Crossman, MD, FRCP; David C. Cumberland, FRCP; Christopher M. Newman, MA, FRCP, PhD

From Cardiovascular Medicine, Division of Clinical Sciences, University of Sheffield (A.L., S.E.F., D.I.T., J.C., D.C. Crossman, D.C. Cumberland, C.M.N.), Sheffield, UK, and Pharmasonics Inc (A.F.B.), Sunnyvale, Calif.

Correspondence to Dr Christopher M. Newman, University of Sheffield Clinical Sciences Centre, Northern General Hospital, Sheffield S5 7AU, UK. E-mail c.newman{at}sheffield.ac.uk

Abstract

Background—Restenosis after percutaneous coronary intervention remains a serious clinical problem. Progress in local gene therapy to prevent restenosis has been hindered by concerns over the safety and efficacy of viral vectors and the limited efficiency of nonviral techniques. This study investigates the use of adjunctive ultrasound to enhance nonviral gene delivery.

Methods and Results—Cultured porcine vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) were transfected with naked or liposome-complexed luciferase reporter plasmid for 3 hours. Ultrasound exposure (USE) for 60 seconds at 1 MHz, 0.4 W/cm², 30 minutes into this transfection period enhanced luciferase activity 48 hours later by 7.5-fold and 2.4-fold, respectively. Luciferase activity after lipofection of ECs was similarly enhanced 3.3-fold by adjunctive USE. USE had no effect on cell viability, although it inhibited VSMC but not EC proliferation.

Conclusions—Adjunctive USE was associated with enhanced transgene expression in VSMCs and ECs and reduced VSMC but not EC proliferation in vitro, which suggests that ultrasound-assisted local gene therapy has potential as an antirestenotic therapy.

Key Words: restenosis • genes • ultrasonics • transfection

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