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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 VI- 7 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? VI- 7 Heparanase is increased in human heart failure Explanted hearts End-stage heart failure (HF) Pro-heparanase Active heparanase VI- 7 Heparanse is increased in response to pressure overload and lipopolysaccharide Lipopolysaccharide (LPS) Aortic banding (AB) VI- 7 Heparanase is expressed in cardiac cells VI- 7 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