Document Detail


Heterozygous disruption of SERCA2a is not associated with impairment of cardiac performance in humans: implications for SERCA2a as a therapeutic target in heart failure.
MedLine Citation:
PMID:  15845614     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To verify whether a deficiency in the cardiac sarcoplasmic reticulum pump SERCA2a causes cardiac dysfunction in humans.
DESIGN: Cardiac performance was measured in a serendipitous human model of primary SERCA2a deficiency, Darier's disease, an autosomal dominant skin disorder caused by mutations inactivating one copy of the ATP2A2 gene, which encodes SERCA2a.
METHODS: Systolic and diastolic function and contractility were assessed by echocardiography at rest and during exercise in patients with Darier's disease with known mutations. Fourteen patients with Darier's disease were compared with 14 normal controls and six patients with dilated cardiomyopathy with stable heart failure.
RESULTS: Resting systolic and diastolic function was normal in patients with Darier's disease and in controls. The increase in systolic function during exercise was not different between patients with Darier's disease and normal controls; neither was there a difference in contractility. As expected, patients with dilated cardiomyopathy had impaired diastolic and systolic function with depressed contractility at rest and during exercise.
CONCLUSION: Contrary to expectations, heterozygous disruption of SERCA2a is not associated with the impairment of cardiac performance in humans. Attempts to increase SERCA2a levels in heart failure, although showing promise in rodent studies, may not be addressing a critical causal pathway in humans.
Authors:
B M Mayosi; A Kardos; C H Davies; F Gumedze; A Hovnanian; S Burge; H Watkins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-04-21
Journal Detail:
Title:  Heart (British Cardiac Society)     Volume:  92     ISSN:  1468-201X     ISO Abbreviation:  Heart     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-20     Completed Date:  2006-02-03     Revised Date:  2012-07-12    
Medline Journal Info:
Nlm Unique ID:  9602087     Medline TA:  Heart     Country:  England    
Other Details:
Languages:  eng     Pagination:  105-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
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MeSH Terms
Descriptor/Qualifier:
Calcium-Transporting ATPases / deficiency,  genetics*
Cardiomyopathy, Dilated / genetics*
Case-Control Studies
Darier Disease / genetics*
Exercise Tolerance
Female
Gene Therapy / methods
Heart Failure / genetics*,  therapy
Heterozygote*
Humans
Male
Middle Aged
Mutation / genetics
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
EC 3.6.3.8/ATP2A2 protein, human; EC 3.6.3.8/Calcium-Transporting ATPases; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases
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