Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury
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 mem...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/15/3426 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Renáta Gáspár |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:08:58Z |
| format | Article |
| id | doaj.art-504202b5d6854673b8b78426b30ec286 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:08:58Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-504202b5d6854673b8b78426b30ec2862023-11-20T08:14:56ZengMDPI AGMolecules1420-30492020-07-012515342610.3390/molecules25153426Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion InjuryRenáta Gáspár0Kamilla Gömöri1Bernadett Kiss2Ágnes Szántai3János Pálóczi4Zoltán V. Varga5Judit Pipis6Barnabás Váradi7Bence Ágg8Tamás Csont9Péter Ferdinandy10Monika Barteková11Anikó Görbe12Metabolic Diseases and Cell Signaling (MEDICS) Research Group, Department of Biochemistry, Interdisciplinary Excellence Centre, University of Szeged, Dom ter 9, H-6720 Szeged, HungaryCardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, HungaryCardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, HungaryCardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, HungaryCardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, HungaryCardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, HungaryPharmahungary Group, Hajnoczy utca 6, H-6722 Szeged, HungaryCardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, HungaryCardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, HungaryMetabolic Diseases and Cell Signaling (MEDICS) Research Group, Department of Biochemistry, Interdisciplinary Excellence Centre, University of Szeged, Dom ter 9, H-6720 Szeged, HungaryCardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvarad ter 4, H-1089 Budapest, HungaryInstitute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, SlovakCardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Szeged, Dom ter 12, H-6720 Szeged, HungarySearch 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.https://www.mdpi.com/1420-3049/25/15/3426cardiac myocytescardio protectionischemia/reperfusion injuryproteoglycandecorin |
| spellingShingle | 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 Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury Molecules cardiac myocytes cardio protection ischemia/reperfusion injury proteoglycan decorin |
| title | Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury |
| title_full | Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury |
| title_fullStr | Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury |
| title_full_unstemmed | Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury |
| title_short | Decorin Protects Cardiac Myocytes against Simulated Ischemia/Reperfusion Injury |
| title_sort | decorin protects cardiac myocytes against simulated ischemia reperfusion injury |
| topic | cardiac myocytes cardio protection ischemia/reperfusion injury proteoglycan decorin |
| url | https://www.mdpi.com/1420-3049/25/15/3426 |
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