Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury
Renáta Gáspár,
Kamilla Gömöri,
Bernadett Kiss,
Ágnes Szántai,
János Pálóczi,
Zoltán V. Varga,
Judit Pipis,
Barnabás Váradi,
Bence Ágg,
Tamás Csont,
Péter Ferdinandy,
Monika Barteková,
Anikó Görbe
Affiliations
Renáta Gáspár
Metabolic Diseases and Cell Signaling (MEDICS) Research Group, Department of Biochemistry, Interdisciplinary Excellence Centre, University of Szeged, Dom ter 9, H-6720 Szeged, Hungary
Kamilla Gömöri
Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, Hungary
Bernadett Kiss
Cardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, Hungary
Ágnes Szántai
Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, Hungary
János Pálóczi
Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, Hungary
Zoltán V. Varga
Cardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, Hungary
Judit Pipis
Pharmahungary Group, Hajnoczy utca 6, H-6722 Szeged, Hungary
Barnabás Váradi
Cardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, Hungary
Bence Ágg
Cardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, Hungary
Tamás Csont
Metabolic Diseases and Cell Signaling (MEDICS) Research Group, Department of Biochemistry, Interdisciplinary Excellence Centre, University of Szeged, Dom ter 9, H-6720 Szeged, Hungary
Péter Ferdinandy
Cardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, Hungary
Monika Barteková
Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovak
Anikó Görbe
Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, Hungary
Search for new cardioprotective therapies is of great importance since no cardioprotective drugs are available on the market. In line with this need, several natural biomolecules have been extensively tested for their potential cardioprotective effects. Previously, we have shown that biglycan, a member of a diverse group of small leucine-rich proteoglycans, enhanced the expression of cardioprotective genes and decreased ischemia/reperfusion-induced cardiomyocyte death via a TLR-4 dependent mechanism. Therefore, in the present study we aimed to test whether decorin, a small leucine-rich proteoglycan closely related to biglycan, could exert cardiocytoprotection and to reveal possible downstream signaling pathways. Methods: Primary cardiomyocytes isolated from neonatal and adult rat hearts were treated with 0 (Vehicle), 1, 3, 10, 30 and 100 nM decorin as 20 h pretreatment and maintained throughout simulated ischemia and reperfusion (SI/R). In separate experiments, to test the mechanism of decorin-induced cardio protection, 3 nM decorin was applied in combination with inhibitors of known survival pathways, that is, the NOS inhibitor L-NAME, the PKG inhibitor KT-5823 and the TLR-4 inhibitor TAK-242, respectively. mRNA expression changes were measured after SI/R injury. Results: Cell viability of both neonatal and adult cardiomyocytes was significantly decreased due to SI/R injury. Decorin at 1, 3 and 10 nM concentrations significantly increased the survival of both neonatal and adult myocytes after SI/R. At 3nM (the most pronounced protective concentration), it had no effect on apoptotic rate of neonatal cardiac myocytes. No one of the inhibitors of survival pathways (L-NAME, KT-5823, TAK-242) influenced the cardiocytoprotective effect of decorin. MYND-type containing 19 (Zmynd19) and eukaryotic translation initiation factor 4E nuclear import factor 1 (Eif4enif1) were significantly upregulated due to the decorin treatment. In conclusion, this is the first demonstration that decorin exerts a direct cardiocytoprotective effect possibly independent of NO-cGMP-PKG and TLR-4 dependent survival signaling.
