Document Detail


A Profibrotic Role for Interleukin-4 in Cardiac Pressure Overload.
MedLine Citation:
PMID:  22492684     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Peter Kanellakis; Michael Ditiatkovski; Gina Kostolias; Alexander Bobik
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-5
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Vascular Biology and Atherosclerosis Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Australia.
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