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. (C) 2002 Elsevier Science (USA). All rights reserved.