Role of early growth response 1 in arteriogenesis: impact on vascular cell proliferation and leukocyte recruitment in vivo

Thromb Haemost. 2012 Mar;107(3):562-74. doi: 10.1160/TH11-07-0490. Epub 2012 Feb 8.


Based on previous findings that early growth response 1 (Egr-1) participates in leukocyte recruitment and cell proliferation in vitro, this study was designed to investigate its mode of action during arteriogenesis in vivo. In a model of peripheral arteriogenesis, Egr-1 was significantly upregulated in growing collaterals of wild-type (WT) mice, both on mRNA and protein level. Egr-1(-/-) mice demonstrated delayed arteriogenesis after femoral artery ligation. They further showed increased levels of monocytes and granulocytes in the circulation, but reduced levels in adductor muscles under baseline conditions. After femoral artery ligation, elevated numbers of macrophages were detected in the perivascular zone of collaterals in Egr-1(-/-) mice and mRNA of leukocyte recruitment mediators was upregulated. Other Egr family members (Egr-2 to -4) were significantly upregulated only in Egr-1(-/-) mice, suggesting a mechanism of counterbalancing Egr-1 deficiency. Moreover, splicing factor-1, downregulated in WT mice after femoral artery ligation in the process of increased vascular cell proliferation, was upregulated in Egr-1(-/-) mice. αSM-actin on the other hand, significantly downregulated in WT mice, showed no differential expression in Egr-1(-/-) mice. While cell cycle regulator cyclin E and cdc20 were upregulated in Egr-1(-/-) mice, cyclin D1 expression decreased below the detection limit in collaterals, and the proliferation marker ki67 was not differentially expressed. In conclusion, compensation for deficiency in Egr-1 function in leukocyte recruitment can presumably be mediated by other transcription factors; however, Egr-1 is indispensable for effective vascular cell cycle progression in arteriogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Growth Processes / genetics
  • Cell Movement
  • Collateral Circulation / genetics
  • Disease Models, Animal
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / immunology
  • Early Growth Response Protein 1 / metabolism*
  • Femoral Artery / metabolism*
  • Femoral Artery / pathology
  • Femoral Artery / surgery
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Granulocytes / pathology
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Monocytes / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Neovascularization, Physiologic / genetics*
  • Neovascularization, Physiologic / immunology
  • Peripheral Arterial Disease / genetics*
  • Peripheral Arterial Disease / immunology
  • Steroidogenic Factor 1 / genetics
  • Steroidogenic Factor 1 / metabolism


  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Steroidogenic Factor 1