Delivery of TFPI-2 using SonoVue and adenovirus results in the suppression of thrombosis and arterial re-stenosis

Abstract

Genes could be used to treat atherosclerosis. The key problem is how to target a gene through the walls of arteries in free-flowing blood. TFPI-2 has been shown to suppress thrombosis and arterial re-stenosis, which indicates its potential function in gene therapy for atherosclerosis. The microbubble ultrasound contrast agent is widely applied in diagnostic imaging, and could be used for transferring genes into arteries. By transfecting TFPI-2 into arteries using SonoVue (a kind of microbubble ultrasound contrast agent), we identified TFPI-2 as an available factor for inhibiting the proliferation of vascular endothelial cells in vivo. Compared with adenovirus, SonoVue showed similar gene transfection efficiency, but the latter showed stronger inhibition of thrombosis and arterial re-stenosis with a high expression of TFPI-2 protein in vitro and in vivo. SonoVue was less damaging when transfecting genes into the arterial wall. These data indicate that transfecting human TFPI-2 into the arterial wall may suppress thrombosis and arterial re-stenosis, and reduce atherosclerosis.