Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-β Type II receptor Academic Article uri icon


MeSH Major

  • Arteriosclerosis
  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Receptors, Transforming Growth Factor beta
  • Transcription Factors


  • Atherosclerotic lesions may progress due to a "failure to die" by vascular repair cells. Egr-1, a zinc finger transcription factor, is elevated more than 5-fold in human carotid lesions relative to the adjacent tunica media. Lesion cells in vitro also express 2-3-fold higher Egr-1 mRNA and protein levels but express much lower levels of the transforming growth factor-beta (TGF-beta) Type II receptor (TbetaR-2) and are functionally resistant to the antiproliferative effects of TGF-beta. Lesion cells fail to express a TbetaR-2 promoter/chloramphenicol acetyltransferase (CAT) construct but overexpress an Egr-1-inducible platelet-derived growth factor-A promoter/CAT construct. Transfection of Egr-1 cDNA represses TbetaR-2/CAT constructs but induces PDGF-A/CAT. Egr-1 transfection reduces the levels of TbetaR-2 and confers resistance to the antiproliferative effect of TGF-beta1. Egr-1 can interact directly with both the -143 Sp1 site and the positive regulatory element 2 (PRE2) (ERT/ets) region of the TbetaR-2 promoter. Thus, although activating a family of stress-responsive genes, Egr-1 also transcriptionally represses one of the major inhibitory pathways that restrains vascular repair.

publication date

  • December 15, 2000



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M005159200

PubMed ID

  • 10982796

Additional Document Info

start page

  • 39039

end page

  • 47


  • 275


  • 50