Heterozygous disruption of SERCA2a is not associated with impairment of cardiac performance in humans: Implications for SERCA2a as a therapeutic target in heart failure

B. M. Mayosi, A. Kardos, C. H. Davies, F. Gumedze, A. Hovnanian, S. Burge, Hugh Watkins

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)105-109
Number of pages5
JournalHeart
Volume92
Issue number1
DOIs
Publication statusPublished - Jan 2006

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Darier Disease
Heart Failure
Dilated Cardiomyopathy
Exercise
Therapeutics
Deficiency Diseases
Mutation
Critical Pathways
Sarcoplasmic Reticulum
Echocardiography
Rodentia
Skin
Genes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Heterozygous disruption of SERCA2a is not associated with impairment of cardiac performance in humans : Implications for SERCA2a as a therapeutic target in heart failure. / Mayosi, B. M.; Kardos, A.; Davies, C. H.; Gumedze, F.; Hovnanian, A.; Burge, S.; Watkins, Hugh.

In: Heart, Vol. 92, No. 1, 01.2006, p. 105-109.

Research output: Contribution to journalArticle

Mayosi, B. M. ; Kardos, A. ; Davies, C. H. ; Gumedze, F. ; Hovnanian, A. ; Burge, S. ; Watkins, Hugh. / Heterozygous disruption of SERCA2a is not associated with impairment of cardiac performance in humans : Implications for SERCA2a as a therapeutic target in heart failure. In: Heart. 2006 ; Vol. 92, No. 1. pp. 105-109.
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