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European Journal of Heart Failure Advance Access originally published online on April 9, 2009
European Journal of Heart Failure 2009 11(6):559-566; doi:10.1093/eurjhf/hfp049
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Upregulated expression of cardiac ankyrin repeat protein in human failing hearts due to arrhythmogenic right ventricular cardiomyopathy

Ying-Jie Wei*, Chuan-Jue Cui, Yin-Xia Huang, Xiao-Lling Zhang, Hao Zhang and Sheng-Shou Hu*

Key Laboratory of Cardiovascular Regenerative Medicine, Chinese Academy of Medical Science, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Ministry of Health, Beijing 100037, People's Republic of China

* Corresponding author. Tel: +86 10 8839 8494, Fax: +86 10 8839 6050, Email: weiyingjiefw{at}126.com (Y.J.W.); shengshouhu{at}yahoo.com (S.S.H.)


   Abstract

Aims: Expression of cardiac ankyrin repeat protein (CARP) is augmented in heart failure due to dilated or ischaemic cardiomyopathy. It is unclear whether CARP is upregulated in heart failure due to arrhythmogenic right ventricular cardiomyopathy (ARVC). In the present study, we investigated the expression pattern of CARP and the correlation between CARP and the well-known heart failure marker pro-atrial natriuretic peptide (proANP) in ARVC failing hearts.

Methods and results: Gene microarray analysis demonstrated increased CARP expression in ARVC failing hearts compared with non-failing control hearts, which was further validated by real-time RT–PCR, western blot, and ELISA at the mRNA and protein levels. Fractionation experiments revealed that the upregulation of CARP expression is restricted to the nuclei of residual cardiac cells in ARVC failing hearts. Regression analysis showed a positive correlation between CARP and proANP in ARVC failing hearts.

Conclusion: Augmented CARP expression may be a common molecular event in failing hearts regardless of cardiomyopathic aetiology. The upregulation of nuclear CARP expression and positive correlation between cardiac CARP and proANP suggests that CARP may be used as a genetic marker existing in the nuclei in contrast to proANP existing in the cytosol of cardiac cells in heart failure patients.

Key Words: Gene microarray • Cardiac ankyrin repeat protein • Arrhythmogenic right ventricular cardiomyopathy • Heart failure • Marker

Received October 13, 2008; Revised February 9, 2009; Accepted February 26, 2009


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