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


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.


CONCLUSIONS
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 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. weiyingjiefw@126.com
Ying-Jie
YJ
Wei
Chuan-Jue
CJ
Cui
Yin-Xia
YX
Huang
Xiao-Lling
XL
Zhang
Hao
H
Zhang
Sheng-Shou
SS
Hu
D000293:Adolescent; D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers; D015153:Blotting, Western; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics*; D055815:Young Adult
C491304:ANKRD1 protein, human; D015415:Biomarkers; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D020930:MAP Kinase Kinase Kinases