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Biglycan protects cardiomyocytes against hypoxia/reoxygenation injury: Role of nitric oxide
Authors:Tamá  s Csont,Anikó    rbe,Erika Bereczki,Eda Aypar,Zoltá  n V. Varga,Ferenc Fü    p,Pé  ter Ferdinandy
Affiliation:a Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary
b Institute of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary
c Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary
d Pharmahungary™ Group, Szeged, Hungary
Abstract:Biglycan, a proteoglycan component of extracellular matrix, has been suspected to contribute to the development of atherosclerosis, but overexpression of biglycan in transgenic mice has been shown to induce cardioprotective genes including nitric oxide (NO) synthases in the heart. Therefore, here we hypothesized if exogenous administration of biglycan exerts cytoprotection. Primary cardiomyocytes from neonatal rats were subjected to 150 min hypoxia and 2 h reoxygenation. Mortality of cardiomyocytes was dose-dependently attenuated by pretreatment with 1-100 nM biglycan. Biglycan enhanced eNOS mRNA and protein, and significantly increased NO content of cardiomyocytes. The NO synthase inhibitor l-nitro-arginine-methyl-ester significantly attenuated the cytoprotective effect of biglycan. This is the first demonstration that biglycan leads to cytoprotection against hypoxia/reoxygenation injury, and that this phenomenon is partially mediated by an NO-dependent mechanism.
Keywords:Cytoprotection   Biglycan   Proteoglycans   Nitric oxide   Hypoxia/reoxygenation   Myocytes
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