| Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling. | |
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MedLine Citation:
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PMID: 20177000 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The evolutionary conserved Wnt signaling pathway regulates cardiogenesis. However, members of the Wnt pathway are also expressed in the adult heart. Although Wnt-signaling is quiescent under normal conditions, we noticed activation on pathological stress of the heart, such as chronic afterload increase. To examine the role of Wnt signaling on the postnatal heart, we modified the expression and function of the Wnt regulator dishevelled 1 (Dvl-1) both in transgenic mice with cardiac-specific overexpression of Dvl-1 (Dvl-1-Tg) and in cultured cardiac myocytes. Dvl-1-Tg mice (3 months) had severe cardiac hypertrophy (heart weight:body weight ratio: 5.2+/-0.3 mg/g wild-type [WT] versus 6.4+/-0.7 mg/g Dvl-1-Tg; P<0.01), an increase in cardiomyocyte size (86% increase in Dvl-1-Tg compared with WT; P<0.01) and marked raise of atrial natriuretic factor expression (12-fold increase versus WT; P<0.01). Hypertrophy was associated with left ventricular dilatation in Dvl-1-Tg and a reduction of ejection fraction (4.4+/-0.1 mm versus 5.5+/-0.2 mm, 80+/-2% and 43+/-4% in WT versus Dvl-1-Tg, respectively; P<0.01). Transgenic animals died prematurely before 6 months of age. Both canonical as well as noncanonical Wnt signaling branches were activated in the Dvl-1-Tg animals. Small interfering RNA-mediated depletion of Dvl-1 was used to further characterize the role of Dvl-1 in cardiac myocytes. Whereas baseline parameters were unaltered, beta-adrenergic hypertrophic response was abrogated in Dvl-1 knockdown cardiac myocytes, indicating a mandatory role in beta-adrenergic stimulation. Therefore, activation of Wnt signaling is sufficient and critical for the induction of myocardial hypertrophy and cardiomyopathy. |
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Authors:
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Pratima Malekar; Marco Hagenmueller; Adamma Anyanwu; Sebastian Buss; Marcus R Streit; Celine S Weiss; David Wolf; Johannes Riffel; Alexander Bauer; Hugo A Katus; Stefan E Hardt |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-22 |
Journal Detail:
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Title: Hypertension Volume: 55 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-18 Completed Date: 2010-04-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 939-45 Citation Subset: IM |
Affiliation:
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Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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genetics,
metabolism* Analysis of Variance Animals Apoptosis / genetics Blotting, Western Cardiomegaly / genetics, metabolism*, pathology Cells, Cultured Echocardiography Heart / physiopathology Heart Failure / genetics, metabolism*, pathology Mice Mice, Transgenic Myocardial Contraction / genetics Myocardium / metabolism, pathology Myocytes, Cardiac / metabolism, pathology Phosphoproteins / genetics, metabolism* Signal Transduction / physiology Ventricular Remodeling / physiology* Wnt Proteins / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Phosphoproteins; 0/Wnt Proteins; 0/dishevelled proteins |
| Comments/Corrections | |
Comment In:
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Hypertension. 2010 Apr;55(4):852-4
[PMID:
20176999
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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