Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction
| Autor: | Frans Van de Werf, Peter Carmeliet, Melissa Swinnen, Stephane Heymans, E. Helene Sage, Jan D'hooge, Jack P.M. Cleutjens, Yigal M. Pinto, Rick van Leeuwen, Jacques Debets, Mark W.M. Schellings, Davy Vanhoutte |
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| Přispěvatelé: | ACS - Amsterdam Cardiovascular Sciences, Cardiology |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Myocardial Infarction heart failure Smad2 Protein 030204 cardiovascular system & hematology Extracellular matrix Mice 0302 clinical medicine Transforming Growth Factor beta Immunology and Allergy Osteonectin Mice Knockout Extracellular Matrix Proteins 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction Matricellular protein Granulation tissue Heart Articles 3. Good health myocardial infarction medicine.anatomical_structure Female adenoviral overexpression Signal Transduction medicine.medical_specialty Immunology Article 03 medical and health sciences Internal medicine medicine Animals Heart Rupture Post-Infarction 030304 developmental biology transforming growth factor-beta signaling business.industry Myocardium Calcium-Binding Proteins Cardiac Rupture Hemodynamics collagen remodeling Transforming growth factor beta Fibroblasts Survival Analysis Rats Mice Inbred C57BL Endocrinology Rats Inbred Lew Granulation Tissue biology.protein Wound healing business Transforming growth factor |
| Zdroj: | Journal of experimental medicine, 206(1), 113-123. Rockefeller University Press The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | 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. ispartof: JOURNAL OF EXPERIMENTAL MEDICINE vol:206 issue:1 pages:113-123 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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