PMID- 22492684
OWN - NLM
STAT- MEDLINE
DCOM- 20121023
LR  - 20220310
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 95
IP  - 1
DP  - 2012 Jul 1
TI  - A pro-fibrotic role for interleukin-4 in cardiac pressure overload.
PG  - 77-85
LID - 10.1093/cvr/cvs142 [doi]
AB  - 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 
      pro-fibrotic in the liver and the 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.
FAU - Kanellakis, Peter
AU  - Kanellakis P
AD  - Vascular Biology and Atherosclerosis Laboratory, BakerIDI Heart and Diabetes 
      Institute, St Kilda Road Central, Melbourne, VIC 8008, Australia.
FAU - Ditiatkovski, Michael
AU  - Ditiatkovski M
FAU - Kostolias, Gina
AU  - Kostolias G
FAU - Bobik, Alexander
AU  - Bobik A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120405
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transforming Growth Factor beta)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - Aortic Coarctation/etiology
MH  - Cell Proliferation
MH  - Fibrosis
MH  - Hypertension/*pathology
MH  - Interleukin-4/*physiology
MH  - Macrophages/physiology
MH  - Male
MH  - Mast Cells/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/*pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Transforming Growth Factor beta/physiology
EDAT- 2012/04/12 06:00
MHDA- 2012/10/24 06:00
CRDT- 2012/04/12 06:00
PHST- 2012/04/12 06:00 [entrez]
PHST- 2012/04/12 06:00 [pubmed]
PHST- 2012/10/24 06:00 [medline]
AID - cvs142 [pii]
AID - 10.1093/cvr/cvs142 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2012 Jul 1;95(1):77-85. doi: 10.1093/cvr/cvs142. Epub 2012 Apr 5.