Document Detail


Up-regulation of connexin45 in heart failure.
MedLine Citation:
PMID:  14678136     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Heart failure is associated with reduced expression of the major gap junction protein connexin43 (Cx43), which may contribute to arrhythmias and sudden cardiac death in this patient population. Other cardiac connexins may be altered as well. Because connexin45 (Cx45) has been shown to colocalize with Cx43, we determined whether the number, size, or distribution of Cx45 gap junctions is altered in the failing heart. METHODS AND RESULTS: Cx45 expression levels were measured by immunoblotting and quantitative immunostaining in failing and control human left ventricles. Total Cx45 protein was significantly (P = 0.021) up-regulated 1.8-fold in failing hearts. Cx45 immunohistochemical signal was increased by 80% (P = 0.005) due to a 3.5-fold increase in the number of gap junctions containing Cx45. Cx45 mRNA was not altered in failing hearts, suggesting reduced degradation of Cx45 protein in the failing heart. Cx43 signal, on the other hand, was reduced by 49% in failing hearts. Double-label experiments demonstrated colocalization of Cx45 and Cx43 in the same gap junctions. CONCLUSION: Cx45 is markedly enhanced in the failing heart. Up-regulation of Cx45 in conjunction with down-regulation of Cx43 could result in abnormal impulse propagation and generation of ventricular arrhythmias, thereby predisposing patients in heart failure to sudden cardiac death.
Authors:
Kathryn A Yamada; Joseph G Rogers; Rune Sundset; Thomas H Steinberg; Jeffrey E Saffitz
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular electrophysiology     Volume:  14     ISSN:  1045-3873     ISO Abbreviation:  J. Cardiovasc. Electrophysiol.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-12-17     Completed Date:  2004-04-13     Revised Date:  2010-05-26    
Medline Journal Info:
Nlm Unique ID:  9010756     Medline TA:  J Cardiovasc Electrophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1205-12     Citation Subset:  IM    
Affiliation:
Department of Medicine (Cardiovascular Division), Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. kyamada@im.wustl.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Connexin 43 / metabolism*
Connexins / metabolism*
Female
Heart Failure / complications,  metabolism*
Heart Ventricles / metabolism*
Humans
Male
Middle Aged
Reference Values
Up-Regulation*
Ventricular Dysfunction, Left / etiology,  metabolism*
Grant Support
ID/Acronym/Agency:
HL 50598/HL/NHLBI NIH HHS; HL 58507/HL/NHLBI NIH HHS; HL 66350/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Connexin 43; 0/Connexins; 0/connexin 45
Comments/Corrections
Comment In:
J Cardiovasc Electrophysiol. 2003 Nov;14(11):1213-4   [PMID:  14678137 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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