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Overexpression of Egr‐1 is associated with dilated cardiomyopathy and induces cardiac cell apoptosis
Author(s) -
Lucas Trevor,
Kovatchki Daniel,
Abraham Dietmar,
Schaefer Romana,
Hofer Erhard,
Aharinejad Seyedhossein
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a13-a
Subject(s) - dilated cardiomyopathy , apoptosis , cardiology , medicine , cardiomyopathy , chemistry , heart failure , biochemistry
Idiopathic dilated cardiomyopathy (DCM) is characterized by declined left ventricular ejection fraction, systolic and diastolic dysfunction, ventricular wall remodeling and an increased incidence of apoptosis. The early growth response gene Egr‐1 is a transcription factor containing zinc finger DNA‐binding motifs and domains which both activate and repress transcription from target promoters. In a targeted screen of gene expression levels in DCM cardiac tissue, we found that Egr‐1 expression is significantly increased in DCM patients. An associated increase in the expression levels of the pro‐apoptotic SIVA gene was observed and multiple high affinity and GC rich Egr‐1 binding sites in the promoter region were identified in silico . Adenoviral‐mediated Egr‐1 (AdEgr‐1) overexpression directly induced caspase‐dependent apoptosis in mixed cardiac cultures in vitro which was characterized by surface phosphatidylserine expression, development of a sub G 0 /G 1 population in FACS analysis and the emergence of TUNEL positive nuclei. Induction of apoptosis was accompanied by upregulation of SIVA protein expression in vitro . Direct intracardial injection of AdEgr‐1 also induced rat cardiac apoptosis in vivo . These results indicate that sustained Egr‐1 expression induces a pro‐apoptotic transcriptional program in cardiac cells which may play a pivotal role in the development of DCM.