An Egr-1 master switch for arteriogenesis: studies in Egr-1 homozygous negative and wild-type animals

J Thorac Cardiovasc Surg. 2006 Jan;131(1):138-45. doi: 10.1016/j.jtcvs.2005.08.052. Epub 2005 Dec 5.


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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Occlusive Diseases / therapy
  • Arteries / physiology*
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / physiology*
  • Genetic Therapy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology*
  • Rats
  • Rats, Sprague-Dawley


  • Early Growth Response Protein 1