title: In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia.
abstract: OBJECTIVE
  We examined the relative contributions of inflammation and arterial injury to neointimal formation in a porcine coronary overstretch restenosis model.
  
  
  BACKGROUND
  Previous studies established that stents cause neointimal proliferation proportional to injury. Although inflammation has been postulated to be a major contributor to restenosis after angioplasty, there is a paucity of data on the relation between inflammation and subsequent neointimal formation.
  
  
  METHODS
  Twenty-one pigs underwent balloon injury followed by implantation of oversized, tubular, slotted stents (stent/artery ratio 1.2:1) in the left anterior descending coronary artery. Morphometric analysis of the extent of injury (graded as injury score 0 to 3) and inflammation (graded as inflammation score 0 to 3) 1 month later was assessed and correlated with neointimal formation.
  
  
  RESULTS
  An inflammatory reaction was observed in 20 of 21 pigs, and significant positive correlations were found between the degree of arterial injury and the extent of the inflammatory reaction (r = 0.80, p < 0.01) and between the extent of inflammatory reaction and the neointimal thickness (r = 0.75, p < 0.01), neointimal area (r = 0.53, p = 0.01) and percent area stenosis (r = 0.66, p < 0.01) within the stents. Importantly, there were areas with inflammation only in the absence of injury, and vice versa, that were also associated with neointimal hyperplasia.
  
  
  CONCLUSIONS
  These data suggest that the inflammatory reaction plays an equally important role as arterial injury in neointimal formation after coronary stenting, and that anti-inflammatory approaches may be of value to reduce in-stent restenosis.
authors.affiliation: Department of Internal Medicine (Cardiology Division) and Medlantic Research Institute of the Washington Hospital Center, DC, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kornowski
authors.forename: M K
authors.initials: MK
authors.lastname: Hong
authors.forename: F O
authors.initials: FO
authors.lastname: Tio
authors.forename: O
authors.initials: O
authors.lastname: Bramwell
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: M B
authors.initials: MB
authors.lastname: Leon
mesh_terms: D000818:Animals; D002455:Cell Division; D003251:Constriction, Pathologic; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D006965:Hyperplasia; D007249:Inflammation / Q000473:pathology; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology*