Suppression of neo-intimal hyperplasia induced by arteriovenous anastomosis and balloon-injury in rat by multimeric TRAIL

Abstract Tumor necrosis factor-related apoptosis inducing factor (TRAIL) has shown to play a key role in tumor surveillance, autoimmune diseases, and apoptosis, but its role in vascular stenosis is controversial. In this study, the recombinant hexameric soluble TRAIL (referred as ILz(6):TRAIL), which contains the 6xHis tag, the isoleucine zipper hexamerization domain (ILz), and the extracellular region of TRAIL, inhibits the proliferation of SMemb+/CRBP-1+ vascular smooth muscle cells induced by anastomosis of a carotid artery and a jugular vein (AAV) or balloon injury of femoral artery in rats. Treatment with recombinant ILz(6):TRAIL significantly inhibited the occlusive progress of neo-intimal hyperplasia induced by AAV in a dosage-dependent manner, and adenovirus expressing secretable ILz(6):TRAIL also inhibits neo-intima hyperplasia induced by balloon injury in femoral artery of rats. Furthermore, this inhibitory effect of recombinant ILz(6):TRAIL was associated with the up-regulation of active caspase-3 in vascular smooth muscle cells in AAV regions. Surprisingly, the occlusions of vessels induced by AAV was partially reversed by recombinant ILz(6):TRAIL. This results demonstrates the preventive and partial regressive effects of ILz(6):TRAIL on AAV- or balloon-induced neo-intimal hyperplasia.