K Krasinski1, I Spyridopoulos, M Kearney, D W Losordo. 1. Division of Cardiovascular Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Tumor necrosis factor-alpha (TNF) is expressed locally in arteries at sites of balloon injury. In vitro studies have shown that TNF inhibits cell cycle progression and induces apoptosis in endothelial cells. Accordingly, we performed a series of experiments to test the hypothesis that inhibiting TNF could accelerate endothelial recovery after angioplasty. METHODS AND RESULTS: TNF soluble receptor (TNFsr) has been shown to neutralize the actions of TNF in vitro and in vivo. Sprague-Dawley rats received TNFsr versus control IgG through an intraperitoneal injection. De-endothelializing balloon injury was then performed, and animals were killed after 1 week to evaluate re-endothelialization (Evans blue dye staining) and after 2 weeks to evaluate re-endothelialization and endothelial function. At both time points, blockade of TNF using TNFsr resulted in an increase in re-endothelialization, as measured as absolute area and percent area re-endothelialized. TNFsr also accelerated functional endothelial recovery, which manifest as an increase in nitric oxide production. Neointimal thickening was also shown inhibited. CONCLUSIONS: In vivo blockade of TNF accelerates functional endothelial recovery 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.
BACKGROUND:Tumor necrosis factor-alpha (TNF) is expressed locally in arteries at sites of balloon injury. In vitro studies have shown that TNF inhibits cell cycle progression and induces apoptosis in endothelial cells. Accordingly, we performed a series of experiments to test the hypothesis that inhibiting TNF could accelerate endothelial recovery after angioplasty. METHODS AND RESULTS:TNF soluble receptor (TNFsr) has been shown to neutralize the actions of TNF in vitro and in vivo. Sprague-Dawley rats received TNFsr versus control IgG through an intraperitoneal injection. De-endothelializing balloon injury was then performed, and animals were killed after 1 week to evaluate re-endothelialization (Evans blue dye staining) and after 2 weeks to evaluate re-endothelialization and endothelial function. At both time points, blockade of TNF using TNFsr resulted in an increase in re-endothelialization, as measured as absolute area and percent area re-endothelialized. TNFsr also accelerated functional endothelial recovery, which manifest as an increase in nitric oxide production. Neointimal thickening was also shown inhibited. CONCLUSIONS: In vivo blockade of TNF accelerates functional endothelial recovery 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.
Authors: Amir Aziz; Natalie J Haywood; Paul A Cordell; Jess Smith; Nadira Y Yuldasheva; Anshuman Sengupta; Noman Ali; Ben N Mercer; Romana S Mughal; Kirsten Riches; Richard M Cubbon; Karen E Porter; Mark T Kearney; Stephen B Wheatcroft Journal: Endocrinology Date: 2018-02-01 Impact factor: 4.736