title: In vivo blockade of tumor necrosis factor-alpha accelerates functional endothelial recovery after balloon angioplasty.
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.
  
  
  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.affiliation: Division of Cardiovascular Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: K
authors.initials: K
authors.lastname: Krasinski
authors.forename: I
authors.initials: I
authors.lastname: Spyridopoulos
authors.forename: M
authors.initials: M
authors.lastname: Kearney
authors.forename: D W
authors.initials: DW
authors.lastname: Losordo
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007074:Immunoglobulin G / Q000008:administration & dosage; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics; D020127:Recovery of Function / Q000187:drug effects*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D017539:Tunica Intima / Q000187:drug effects / Q000293:injuries / Q000473:pathology
chemical_list: D015703:Antigens, CD; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide