Cardiac ankyrin repeat protein, a negative regulator of cardiac gene expression, is augmented in human heart failure.
The technique of representational difference analysis of cDNA has been applied to screen for differentially expressed genes in a canine model of pacing-induced heart failure. We identified the canine homolog of the cardiac ankyrin repeat protein (CARP) which has been shown to be involved in the regulation of the transcription of cardiac genes. To confirm the significance for human heart failure, cardiac tissue specimens obtained from non-failing donor hearts and from explanted hearts from patients with end-stage heart failure were investigated. CARP mRNA and protein levels were markedly increased in failing left ventricles. Interestingly, alterations in CARP expression were restricted to ventricular tissue and were not observed in atria. Fractionation experiments revealed that CARP was expressed predominantly in the nuclei consistent with the proposed function of CARP as a modulator of transcription. Together, these findings raise the possibility that augmented ventricular CARP expression may play a role in the pathogenesis of human heart failure.
Zolk
Oliver
O
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstr. 17, 91054 Erlangen, Germany. zolk@pharmakologie.uni-elargen.de
Frohme
Marcus
M
Maurer
Alexander
A
Kluxen
Franz-Werner
FW
Hentsch
Bernd
B
Zubakov
Dimitri
D
Hoheisel
Jörg D
JD
Zucker
Irving H
IH
Pepe
Salvatore
S
Eschenhagen
Thomas
T
D000328:Adult; D000368:Aged; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004285:Dogs; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*
C491304:ANKRD1 protein, human; D018076:DNA, Complementary; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D012313:RNA