| Blocking of Frizzled Signaling With a Homologous Peptide Fragment of Wnt3a/Wnt5a Reduces Infarct Expansion and Prevents the Development of Heart Failure After Myocardial Infarction. | |
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MedLine Citation:
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PMID: 21931076 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background-The molecular pathways that control the wound healing after myocardial infarction (MI) are not completely elucidated. One of these pathways is the Wnt/Frizzled pathway. In this study, we evaluated Frizzled as a novel therapeutic target for MI. These Frizzled proteins act as receptors for Wnt proteins and were previously shown to be expressed in the healing infarct.Methods and Results-Wnt/Frizzled signaling has been studied for decades, but synthetic ligands that interfere with the interaction between Wnts and Frizzled have not been described to date. Here we report the selection of 3 peptides derived from regions of high homology between Wnt3a and Wnt5a that act as antagonists for Frizzled proteins. UM206, the peptide with the highest affinity, antagonized the effect of Wnt3a and Wnt5a in different in vitro assays. Administration of UM206 to mice for 5 weeks, starting immediately after the induction of MI, reduced infarct expansion and increased the numbers of capillaries and myofibroblasts in the infarct area. Moreover, heart failure development was inhibited by this therapy.Conclusions-Blocking of Frizzled signaling reduces infarct expansion and preserves cardiac function after MI. Our findings underscore the potential of Frizzled receptors as a target for pharmacotherapy of cardiac remodeling after MI. |
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Authors:
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Hilde Laeremans; Tilman M Hackeng; Marc A M J van Zandvoort; Victor L J L Thijssen; Ben J A Janssen; Harry C J Ottenheijm; Jos F M Smits; W Matthijs Blankesteijn |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-19 |
Journal Detail:
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Title: Circulation Volume: - ISSN: 1524-4539 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Departments of Pharmacology, Biochemistry, and Biomedical Engineering, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands; and Angiogenesis Laboratory, Department of Radiotherapy and Medical Oncology, VU Medical Center, Amsterdam, Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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