Tumor necrosis factor-α antibody eluting stents reduce vascular smooth muscle cell proliferation in saphenous vein organ culture

Expression of TNF-alpha a vascular smooth muscle cell (VSMC) mitogen. is up-regulated in injured/proliferating vessel wall. Coronary stents are tested worldwide for their use as local drug delivery devices to address vascular pathophysiology. In this study we have investigated the effect of TNF-alpha antibody eluting stents on VSMC proliferation in human saphenous vein (HSV) organ Culture. The adsorption and elution characteristics of TNF-alpha antibody was assessed using stent wires. The stents adsorbed up to 0.25 mug of TNF-alpha antibody/mg of stent and showed a biexponential elution curve, with 34.4% (SD 4.4%) antibody remaining on the stent after 72 h of washing in a perfusion circuit. TNF-alpha antibody delivery from loaded stents to the vessel wall was assessed ex vivo. TNF-alpha and proliferating cell nuclear antigen (PCNA) expression in the vascular specimens was assessed by immunostaining or ELISAs. TNF-alpha ELISAs showed a significant increase in the cytokine levels from the vascular lysates prepared from proliferating tissue culture compared with fresh vein (P < 0.05). Immunohistochemical localization showed an increase in the PCNA positivity of VSMC from these cultures. PCNA staining was barely detected from the fresh tissue. However, a decrease in PCNA staining was observed from tissue sections of venous segments cultured with TNF-alpha antibody eluting, stents. PCNA ELISAs demonstrated a 23.7% decline in the antigen levels from the day 7 tissue cultured with such loaded stems. In conclusion, activated VSMC in tissue culture showed an up-regulation of TNF-alpha cytokine. in association with an increase in the PCNA expression in the vessel wall. The local neutralization of this cytokine with TNF-alpha antibody eluting stents reduced VSMC proliferation in the wall. We suggest that TNF-alpha antibody eluting stents may limit restenosis in vivo, which may have important clinical benefits. (C) 2002 Elsevier. Science (USA).