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VI- 7
The heparanase-syndecan-4 axis
in the heart: upregulation in response to
immune activation indicates a role in cardiac
inflammation
Mari Elen Strand1,2, Jan Magnus Aronsen3, Biljana Skrbic1,2,4, Monika
Gelazauskaite1,2, Ivar Sjaastad1,2, Geir Christensen1,2, Ida G. Lunde IG1,2
1 Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
2 Center for Heart Failure Research, University of Oslo, Oslo, Norway.
3 Bjørknes College, Oslo, Norway.
4 Department of Cardiothoracic Surgery, Oslo University Hospital Ullevål, Oslo, Norway.
14th Annual CHFR Symposium
September 22, 2016
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Background: syndecan-4 in the heart
 The shed heparan sulfate-substituted
ectodomain of syndecan-4 is an
effector of cardiac immune responses,
promoting immune cell recruitment
and extracellular matrix remodeling
HEPARANASE
SYNDECAN-4
Strand et al., FEBS J. 280 (2013) 2228-47
Strand et al., J Mol Cell Cardiol. 88 (2015) 133-44
IS HEPARANASE UPREGULATED
IN FAILING HEARTS?
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Heparanase is increased in human heart failure
Explanted hearts
End-stage heart failure
(HF)
Pro-heparanase
Active heparanase
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Heparanse is increased in response to pressure
overload and lipopolysaccharide
Lipopolysaccharide
(LPS)
Aortic
banding
(AB)
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Heparanase is expressed in cardiac cells
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Summary
 Heparanase is upregulated in failing human hearts, and is induced
alongside syndecan-4 in response to immune activation in mouse
models (AB and LPS)
 Attenuated heparanase mRNA in sdc4KO mice and accentuated
heparanase levels in sdc4Tg mice points to an association between
cardiac levels of syndecan-4 and heparanase
 At baseline, heparanase is more highly expressed in cultured
cardiomyocytes, but is robustly increased in response to inflammatory
signals in cardiac fibroblasts
 Heparanase may play a role in cardiac inflammation,
possibly by regulating aspects of syndecan-4-mediated
immune responses