| A Profibrotic Role for Interleukin-4 in Cardiac Pressure Overload. | |
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MedLine Citation:
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PMID: 22492684 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIMS: The mechanisms underlying cardiac fibrosis in hypertension are yet to be defined although inflammatory cells, fibroblasts and cytokines have been implicated. Here we investigated the role of interleukin-4 (IL-4) in cardiac fibrosis which is elevated in the hypertensive heart. IL-4 has been shown to be profibrotic in liver and lung but its role in cardiac fibrosis has not been investigated. METHODS AND RESULTS: Cardiac fibrosis was induced in mice by constricting the aorta between the two carotid arteries. Fourteen days later marked left ventricular fibrosis developed together with expression of IL-4. Anti-IL-4 neutralizing antibodies attenuated this fibrosis without affecting blood pressure or expression of the transforming growth factor-beta system. The reduction in fibrosis was associated with reductions in interstitial fibroblasts and macrophages together with reductions in proliferating cells and expression of monocyte chemoattractant protein-1 (MCP-1). Since mast cells are a source of IL-4, we also assessed their role in fibrosis. Cromolyn, a mast cell inhibitor attenuated mast cell degranulation as well as IL-4 mRNA expression and cardiac fibrosis without affecting blood pressure. Treatment with Cromolyn also reduced interstitial fibroblasts and macrophages in regions of developing fibrosis as well MCP-1 expression. CONCLUSION: This study demonstrates for the first time that IL-4, most likely produced by mast cells in the heart during pressure overload, is a significant contributor to cardiac fibrosis. Targeting this cytokine may be a useful therapeutic strategy to limit cardiac fibrosis. |
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Authors:
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Peter Kanellakis; Michael Ditiatkovski; Gina Kostolias; Alexander Bobik |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-5 |
Journal Detail:
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Title: Cardiovascular research Volume: - ISSN: 1755-3245 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Vascular Biology and Atherosclerosis Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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