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European Journal of Heart Failure 2004 6(2):161-172; doi:10.1016/j.ejheart.2003.11.004
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© 2003 European Society of Cardiology

Left–right asymmetric ventricular expression of CARP in the piglet heart: regional response to experimental heart failure{star}

Mario Torradoa, Eduardo Lópezb, Alberto Centenob, Alfonso Castro-Beirasb and Alexander T. Mikhailova,*

a Developmental Biology Unit, Institute of Health Sciences University of La Coruña, Campus de Oza, Building ‘El Fortín’, Las Xubias s/n, La Coruña 15006, Spain
b University Hospital ‘Juan Canalejo’ Las Xubias de arriba 58, La Coruña 15006, Spain

* Corresponding author. Tel.: +34-981-167-000; fax: +34-981-138-714. E-mail address: margot{at}udc.es


   Abstract

Background and aim: Cardiac ankyrin repeat protein (CARP), whose expression is down-regulated in response to doxorubicin (Dox) in vitro, has been proposed to be a marker of experimentally-induced cardiac hypertrophy in rodent models. In piglets, the rapid hypertrophy rate of the left ventricle (LV) as compared to that of the right ventricle (RV) represents a natural model of asymmetric ventricular enlargement. We tested whether CARP expression correlates with postnatal ventricular hypertrophy and to what extent CARP can be sensitive to Dox treatment in vivo.

Methods: CARP mRNA and protein levels were quantified (by Northern blot hybridization, semi-quantitative RT-PCR and Western blot) in the piglet heart, both during early postnatal development and upon Dox-induced cardiomyopathy (Dox-CM).

Results: The study revealed: (1) significantly augmented CARP mRNA and protein levels in the LV compared to the RV resulting in left vs. right asymmetry in ventricular CARP expression throughout early postnatal development; (2) dose- and chamber-dependent CARP mRNA and protein enrichment in ventricular myocardium in response to Dox; and (3) abolishment of asymmetric patterns of ventricular CARP expression at heart failure resulting from Dox-CM.

Conclusions: (1) CARP is differentially regulated in the LV and RV during both postnatal development and disease; and (2) monitoring of ventricular CARP expression patterns can be used for further analysis of transition from compensated to overt heart failure.

Key Words: Cardiac left–right asymmetry • Gene expression • CARP • Heart failure • Cardiomyopathy • Doxorubicin

Received May 15, 2003; Revised July 15, 2003; Accepted November 12, 2003


{star} For detailed access on porcine CARP domain structure, CARP dimer formation, design of the Dox treatment protocol, and cardiac parameters of control and Dox-treated piglets see the online-only Figure Supplement Data (Fig. 6, 7 and 8) at http://www.elsevier.com/locate/ejheart.


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