Titre :
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Distinctive troponin-tropomyosin molecular phenotypes associated with acquired DCM, familial DCM and familial HCM (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Marston S ;
Messer A ;
Mirza M ;
Watkins H ;
Redwood C ;
Robinson P
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 204
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Langues:
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Anglais
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Mots-clés :
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cardiomyopathie dilatée
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cardiomyopathie dilatée familiale
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cardiomyopathie hypertrophique familiale
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colloque
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Escherichia coli
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insuffisance cardiaque
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myocarde
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tropomyosine
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troponine
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Résumé :
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Communication n° 245 In failing heart muscle there is a defect in contractility due to dysfunction of the contractile apparatus. In previous studies we identified a specific functional defect in the thin filament regulatory protein troponin extracted from failing heart which could account for the contractile defect. Mutations in troponin and tropomyosin have also been shown to cause familial hypertrophic cardiomyopathy and familial dilated cardiomyopathy. We have investigated troponin -tropomyosin regulatory function in these three pathologies using troponin and tropomyosin extracted from normal and failing myocardium or wild-type and mutant troponin or tropomyosin expressed in e.coli. Regulatory function was studied using a quantitative in vitro motility assay. We compared troponin from 8 donor hearts and 4 myectomy samples with 12 failing hearts and we compared 6 different HCM mutations and 8 DCM mutations with wild-type troponin-tropomyosin. We found a consistent molecular phenotype associated with each pathology. HCM mutations cause higher crossbridge turnover rate and higher Ca2+-sensitivity, DCM mutations caused lower crosbridge turnover rate and lower Ca2+-sensitivity. Acquired DCM was associated with slower crossbridge turnover and higher Ca2+-sensitivity.
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