Early growth responsive gene (Egr)-1 expression correlates with cardiac allograft rejection.
BACKGROUND
Early growth response factor (Egr)-1 is a transcription factor induced by inflammatory cytokines that regulates the expression of cytokines, adhesion molecules, other genes pertinent to inflammatory, and proliferative pathologies. Its expression in allografted tissue and role in the pathogenesis of graft rejection has not been explored. The goal of this work is to determine whether Egr-1 expression could be used as a surrogate marker of cardiac allograft rejection.


METHODS
Egr-1 protein expression was analyzed in endomyocardial biopsies of different rejection grades by immunohistochemistry. Egr-1 mRNA expression was analyzed in 106 biopsies from 11 transplant patients by semiquantitative reverse-transcriptase polymerase chain reaction. Egr-1 was also analyzed in coronary arteries from patients with coronary artery vasculopathy (CAV) by Western blot and immunohistochemistry.


RESULTS
No expression of Egr-1 protein was observed in grade 0 biopsies by immunohistochemistry. Strong nuclear Egr-1 was noted in leukocytes and cardiac myocytes in grade 3 biopsies. A clear pattern emerged where 20% (6/30), 34% (20/58), 22% (2/9), and 89%(8/9) of International Society For Heart and Lung Transplantation grade 0, 1, 2, and 3 biopsies were positive for Egr-1 mRNA. There was a significant (P<0.005) relationship between Egr-1 mRNA expression and rejection grade in endomyocardial biopsies. The calculated odds ratio indicates that a biopsy has a 2.18% greater probability of Egr-1 expression per increasing grade of rejection. Egr-1 was also up-regulated in vascular cells in coronary arteries from patients with CAV.


CONCLUSIONS
In consideration of its role as a transcription factor for genes involved in pathologic processes, Egr-1 expression in endomyocardial biopsies may act as a surrogate marker of cardiac allograft rejection.
Autieri
Michael V
MV
Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Kelemen
Sheri E
SE
Gaughan
John P
JP
Eisen
Howard J
HJ
D015415:Biomarkers; D001706:Biopsy; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015870:Gene Expression; D006084:Graft Rejection / Q000473:pathology* / Q000503:physiopathology*; D016027:Heart Transplantation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics*; D014184:Transplantation, Homologous
D015415:Biomarkers; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors