An Egr-1 master switch for arteriogenesis: studies in Egr-1 homozygous negative and wild-type animals.
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.
Sarateanu
Cristian Sorin
CS
Evanston Northwestern Healthcare, Evanston, Ill, USA.
Retuerto
Mauricio A
MA
Beckmann
James T
JT
McGregor
Leslie
L
Carbray
JoAnn
J
Patejunas
Gerald
G
Nayak
Lina
L
Milbrandt
Jeffrey
J
Rosengart
Todd K
TK
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
D051766:Early Growth Response Protein 1