Document Detail


Diminished zonula occludens-1 expression in the failing human heart.
MedLine Citation:
PMID:  17502245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Reduced expression of the major gap junction protein connexin 43 (Cx43) in the failing human heart may lead to arrhythmias and sudden cardiac death. Cx43 interacts with the actin binding protein, zonula occludens-1 (ZO-1), and it has recently been demonstrated that ZO-1 regulates the formation and function of Cx43 gap junctions. We hypothesize that normal expression of ZO-1 and its interaction with Cx43 are required for appropriate assembly and function of Cx43 gap junctions in the heart. Here, we determined whether expression of ZO-1 is altered in patients with heart failure. METHODS: We examined ventricular myocardium from hearts of patients in end-stage heart failure, obtained at transplant, for ZO-1 expression by immunohistochemistry. We also subjected lysates made from this tissue to immunoblotting to determine the level of ZO-1 expression. RESULTS AND CONCLUSIONS: ZO-1 was found at 96% of the intercalated discs in nonfailing control human hearts, where it colocalized with Cx43. In contrast, there was ZO-1 immunostaining at 5% of intercalated discs in failing hearts, coincident with a reduction in Cx43 staining in intercalated discs. Immunoblotting analysis showed that there was a 95% reduction in ZO-1 expression in human heart failure. Loss of ZO-1 at intercalated discs in heart failure may play a critical role in remodeling of Cx43 gap junctions, which may contribute to abnormal impulse propagation and arrhythmogenesis, thereby predisposing patients in heart failure to sudden cardiac death.
Authors:
James G Laing; Jeffrey E Saffitz; Thomas H Steinberg; Kathryn A Yamada
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-03-21
Journal Detail:
Title:  Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology     Volume:  16     ISSN:  1054-8807     ISO Abbreviation:  Cardiovasc. Pathol.     Publication Date:    2007 May-Jun
Date Detail:
Created Date:  2007-05-15     Completed Date:  2007-07-10     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9212060     Medline TA:  Cardiovasc Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  159-64     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. laing@id.wustl.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Connexin 43 / metabolism
Female
Fluorescent Antibody Technique, Indirect
Heart Failure / metabolism*,  pathology,  physiopathology,  surgery
Heart Transplantation
Heart Ventricles / metabolism*,  pathology
Humans
Male
Membrane Proteins / metabolism*
Middle Aged
Myocardium / metabolism*,  pathology
Phosphoproteins / metabolism*
Grant Support
ID/Acronym/Agency:
DK46686/DK/NIDDK NIH HHS; GM54660/GM/NIGMS NIH HHS; HL66350/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Connexin 43; 0/GJA1 protein, human; 0/Membrane Proteins; 0/Phosphoproteins; 0/zonula occludens-1 protein

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