title: An Egr-1 master switch for arteriogenesis: studies in Egr-1 homozygous negative and wild-type animals.
abstract: BACKGROUND
  Arteriogenesis has been implicated as an important biologic response to acute vascular occlusion. The early growth response 1 (Egr-1) gene encodes an immediate-early response transcription factor that is upregulated by changes in vascular strain and that in turn upregulates a number of putative angiogenic and arteriogenic growth factors. We therefore hypothesized that early growth response 1 might be a critical arteriogenic messenger that induces revascularization in the setting of acute vascular occlusions.
  
  
  METHODS
  Wild-type or Egr-1-/- (null) C57 BL mice, or Sprague-Dawley rats, underwent unilateral iliofemoral artery excision and subsequent analyses for angiogenesis and arteriogenesis through cell-specific immunohistochemistry. Rats were also administered an adenoviral vector encoding for Egr-1 (AdEgr group), noncoding vectors (AdNull group), or saline, after which these animals were assessed by means of serial laser Doppler perfusion imaging and morphologic examination of rat foot-pad ischemic lesions.
  
  
  RESULTS
  Egr-1 wild-type mice demonstrated an equivalent number of capillaries but a greater number of arterioles following excision versus Egr-1 null mice. AdEgr group rats demonstrated greater distal perfusion from 7 to 21 days after excision compared with control animals (P < .02), which approximated normal perfusion at 21 days after excision. AdEgr group rats also demonstrated greater arteriolar density and less severe ischemic foot-pad lesions than control animals.
  
  
  CONCLUSIONS
  These data suggest the importance of Egr-1 as a critical and potentially therapeutic mediator of revascularization after vascular occlusion and implicate arteriogenesis (collateral vessel formation) as a critical component of this process.
authors.affiliation: Evanston Northwestern Healthcare, Evanston, Ill, USA.
authors.forename: Cristian Sorin
authors.initials: CS
authors.lastname: Sarateanu
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Retuerto
authors.forename: James T
authors.initials: JT
authors.lastname: Beckmann
authors.forename: Leslie
authors.initials: L
authors.lastname: McGregor
authors.forename: JoAnn
authors.initials: J
authors.lastname: Carbray
authors.forename: Gerald
authors.initials: G
authors.lastname: Patejunas
authors.forename: Lina
authors.initials: L
authors.lastname: Nayak
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
authors.forename: Todd K
authors.initials: TK
authors.lastname: Rosengart
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000628:therapy; D001158:Arteries / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000502:physiology*; D015316:Genetic Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051766:Early Growth Response Protein 1