In vivo blockade of tumor necrosis factor-alpha accelerates functional endothelial recovery after balloon angioplasty

Background-Tumor necrosis factor-alpha (TNF) is expressed locally in arteri es at sites of balloon injury. In vitro studies have shown that TNF inhibit s cell cycle progression and induces apoptosis in endothelial cells. Accord ingly, we performed a series of experiments to test the hypothesis that inh ibiting TNF could accelerate endothelial recovery after angioplasty. Methods and Results-TNF soluble receptor (TNFsr) has been shown to neutrali ze the actions of TNF in vitro and in vivo. Sprague-Dawley rats received TN Fsr versus control IgG through an intraperitoneal injection. De-endothelial izing balloon injury was then performed, and animals were killed after I we ek to evaluate re-endothelialization (Evans blue dye staining) and after 2 weeks to evaluate re-endothelialization and endothelial function. At both t ime points, blockade of TNF using TNFsr resulted in an increase in re-endot helialization, as measured as absolute area and percent area re-endothelial ized. TNFsr also accelerated functional endothelial recovery, which manifes t as an increase in nitric oxide production. Neointimal thickening was also shown inhibited. Conclusions-In vivo blockade of TNF accelerates functional endothelial reco very after barotraumatic de-endothelializing injury. These findings suggest that locally expressed TNF acts to inhibit functional endothelial recovery after angioplasty and that transient blockade of TNF may improve the long- term success of angioplasty.