| Beta-adrenergic adaptation in paediatric idiopathic dilated cardiomyopathy. | |
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MedLine Citation:
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PMID: 22843448 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BackgroundAlthough the pathophysiology and treatment of adult heart failure (HF) are well studied, HF in children remains poorly understood. In adults, adrenergic receptor (AR)-mediated adaptation plays a central role in cardiac abnormalities in HF, and these patients respond well to β-blocker (BB) therapy. However, in children with HF, there is a growing body of literature suggesting a lack of efficacy of adult HF therapies. Due to these unanticipated differences in response to therapy and the paucity of data regarding the molecular adaptation of the paediatric heart, we investigated the molecular characteristics of HF in children.Methods and resultsExplanted hearts from adults and children with idiopathic dilated cardiomyopathy and non-failing controls were used in the study. Our results show that the molecular characteristics of paediatric HF are strikingly different from their adult counterparts. These differences include: (i) down-regulation of β(1)- and β(2)-AR in children, whereas β(2)-AR expression is maintained in adults; (ii) up-regulation of connexin43 in children, whereas down-regulation is observed in adults; (iii) no differences in phosphatase expression, whereas up-regulation is observed in adults; (iv) no decrease in the phosphorylation of phospholamban at the Ser16 or Thr17 sites in children, which are known characteristics of adult HF.ConclusionThere is a different adaptation of β-AR and adrenergic signalling pathways in children with HF compared with adults. Our results begin to address the disparities in cardiovascular research specific to children and suggest that age-related differences in adaptation could influence the response to therapy. These findings could lead to a paradigm shift in the contemporary management of children with HF. |
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Authors:
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Shelley D Miyamoto; Brian L Stauffer; Stephanie Nakano; Rebecca Sobus; Karin Nunley; Penny Nelson; Carmen C Sucharov |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-26 |
Journal Detail:
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Title: European heart journal Volume: - ISSN: 1522-9645 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-7-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8006263 Medline TA: Eur Heart J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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