Title: Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction
Authors: Schellings, Mark *
Vanhoutte, Davy * ×
Swinnen, Melissa
Cleutjens, Jack
Debets, Jacques
van Leeuwen, Rick
D'hooge, Jan
Van de Werf, Frans
Carmeliet, Peter
Pinto, Yigal
E.Helene, Sage
Heymans, Stephane #
Issue Date: 19-Jan-2009
Publisher: Rockefeller Institute for Medical Research
Series Title: Journal of Experimental Medicine vol:206 issue:1 pages:113-123
Article number: doi:10.1084/jem.20081244
Abstract: The matricellular protein SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin) mediates cell-matrix interactions during wound healing and regulates the production and/or assembly of the extracellular matrix (ECM). This study investigated whether SPARC functions in infarct healing and ECM maturation after myocardial infarction (MI). In comparison with wild-type (WT) mice, animals with a targeted inactivation of SPARC exhibited a fourfold increase in mortality that resulted from an increased incidence of cardiac rupture and failure after MI. SPARC-null infarcts had a disorganized granulation tissue and immature collagenous ECM. In contrast, adenoviral overexpression of SPARC in WT mice improved the collagen maturation and prevented cardiac dilatation and dysfunction after MI. In cardiac fibroblasts in vitro, reduction of SPARC by short hairpin RNA attenuated transforming growth factor beta (TGF)-mediated increase of Smad2 phosphorylation, whereas addition of recombinant SPARC increased Smad2 phosphorylation concordant with increased Smad2 phosphorylation in SPARC-treated mice. Importantly, infusion of TGF-beta rescued cardiac rupture in SPARC-null mice but did not significantly alter infarct healing in WT mice. These findings indicate that local production of SPARC is essential for maintenance of the integrity of cardiac ECM after MI. The protective effects of SPARC emphasize the potential therapeutic applications of this protein to prevent cardiac dilatation and dysfunction after MI.
ISSN: 0022-1007
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cardiology
Vesalius Research Centre (-)
Cardiovascular Imaging and Dynamics
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
* (joint) first author
× corresponding author
# (joint) last author

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