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Osteonectin protects against adverse cardiac inflammation during viral myocarditis
Author(s) -
Papageorgiou Anna,
Rienks Marieke,
Vanhoutte Davy,
Verhesen Wouter,
Carai Paolo,
Vandendriessche Thierry,
Chuah Marinee,
Heymans Stephane
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1128.8
Subject(s) - osteonectin , viral myocarditis , matricellular protein , inflammation , myocarditis , dilated cardiomyopathy , medicine , cardiomyopathy , cardiac function curve , myocyte , endocardium , immunology , biology , heart failure , microbiology and biotechnology , extracellular matrix , biochemistry , alkaline phosphatase , osteocalcin , enzyme
Viral myocarditis is inflammation of the heart muscle as a consequence of infection by common viruses and outcomes for patients range from complete recovery to fatal dilated cardiomyopathy. We investigated the role of the matricellular protein Osteonectin (SPARC) in mitigating the cardiac injury during viral myocarditis. SPARC mRNA and protein expression was induced in the mouse model of viral myocarditis at 7 and 11 days respectively. Under these conditions, SPARC co‐localized with CD‐3‐lymphocytes and VCAM‐endothelial cells. SPARC‐null mice and their wild type (WT) littermates were subjected to human coxsackie‐virusB3 (CVB3)‐induced myocarditis and the absence of SPARC significantly increased cardiac inflammation and mortality as compared to WT mice. We found that SPARC null mice had increased levels of Ly6G+ and Ly6C+ myeloid cells and fewer CD4+ lymphocytes in the heart during viral infection. Importantly, adenoviral overexpression of SPARC in WT animals resulted in improved cardiac function after viral injury as compared to control vector (fractional shortening was 28,2%±0,6 vs 21,2%±0,8 respectively). Collectively these data indicate a role for SPARC in endothelial cell function, leukocyte function and cardiomyocyte contractility. This multifunctional glycoprotein represents an exciting novel target in the treatment of inflammatory heart disease.