title: Endothelial cells overexpressing interleukin-8 receptors reduce inflammatory and neointimal responses to arterial injury.
abstract: BACKGROUND
  Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes bind to IL8 and direct neutrophil recruitment to sites of inflammation, including acutely injured arteries. This study tested whether administration of IL8RA- and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion of ECs to the injured surface, thus suppressing inflammation and neointima formation in balloon-injured rat carotid arteries. We tested the hypothesis that targeted delivery of ECs by overexpressing IL8RA and IL8RB receptors prevents inflammatory responses and promotes structural recovery of arteries after endoluminal injury.
  
  
  RESULTS
  Young adult male rats received balloon injury of the right carotid artery and were transfused intravenously with ECs (total, 1.5×10(6) cells at 1, 3, and 5 hours after injury) transduced with adenoviral vectors carrying IL8RA, IL8RB, and IL8RA/RB (dual transduction) genes, AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs inhibited proinflammatory mediators expression significantly (by 60% to 85%) and reduced infiltration of neutrophils and monocytes/macrophages into injured arteries at 1 day after injury, as well as stimulating a 2-fold increase in reendothelialization at 14 days after injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28 days after injury.
  
  
  CONCLUSIONS
  ECs with overexpression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to injured tissues, preventing inflammation and neointima formation. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 703 19th Street S., Birmingham, AL 35294, USA.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Kaizheng
authors.initials: K
authors.lastname: Gong
authors.forename: Zhengqin
authors.initials: Z
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Hage
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
chemical_list: D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B