The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity
The present study investigated whether Rho-associated protein kinase (RhoA/ROCK) signaling pathway inhibitor simvastatin inhibits matrix metalloproteinase 2 (MMP-2) activity in a rat ischemia-reperfusion injury (I/Ri) model by inhibiting the RhoA/ROCK pathway and reducing <i>MMP-2</i> mR...
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MDPI AG
2022-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/9/1291 |
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| author | Monika Skrzypiec-Spring Agnieszka Sapa-Wojciechowska Alina Rak-Pasikowska Maciej Kaczorowski Iwona Bil-Lula Agnieszka Hałoń Adam Szeląg |
| author_facet | Monika Skrzypiec-Spring Agnieszka Sapa-Wojciechowska Alina Rak-Pasikowska Maciej Kaczorowski Iwona Bil-Lula Agnieszka Hałoń Adam Szeląg |
| author_sort | Monika Skrzypiec-Spring |
| collection | DOAJ |
| description | The present study investigated whether Rho-associated protein kinase (RhoA/ROCK) signaling pathway inhibitor simvastatin inhibits matrix metalloproteinase 2 (MMP-2) activity in a rat ischemia-reperfusion injury (I/Ri) model by inhibiting the RhoA/ROCK pathway and reducing <i>MMP-2</i> mRNA levels. Isolated rat hearts were subjected to aerobic perfusion or I/Ri control. The effect of simvastatin was assessed in hearts subjected to I/Ri. We determined cardiac mechanical function, the content of RhoA, phosphorylated myosin light chain subunit 1 (phospho-MYL9), troponin I, MMP-2, and <i>MMP-2</i> mRNA in the heart homogenates, as well as MMP-2 activity in heart tissue. We showed that treatment with simvastatin caused improvement in the contractile function of the heart subjected to I/Ri which was accompanied by a decrease of MMP-2 activity in heart tissue along with inhibition of RhoA pathway, expressed in a reduction in both RhoA and its downstream product—phosphorylated myosin light chain (phospho-MYL9) in hearts treated with simvastatin. MMP-2 inactivation is not due to inhibition of <i>MMP-2</i> m-RNA synthesis caused by inhibition of RhoA/ROCK pathway and is due, at least in part, to the direct drug action. The protective effect of simvastatin on systolic function in the acute ischemia-reperfusion model does not appear to be related to reduced MMP-2 activation, but other mechanisms related with the inhibition RhoA/ROCK pathway. |
| first_indexed | 2024-03-10T00:36:31Z |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T00:36:31Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8f103365612a4c67861594cd7bef07ed2023-11-23T15:16:14ZengMDPI AGBiomolecules2218-273X2022-09-01129129110.3390/biom12091291The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 ActivityMonika Skrzypiec-Spring0Agnieszka Sapa-Wojciechowska1Alina Rak-Pasikowska2Maciej Kaczorowski3Iwona Bil-Lula4Agnieszka Hałoń5Adam Szeląg6Department of Pharmacology, Wrocław Medical University, 50-345 Wrocław, PolandDepartment of Clinical Chemistry, Wrocław Medical University, 50-556 Wrocław, PolandDepartment of Clinical Chemistry, Wrocław Medical University, 50-556 Wrocław, PolandDepartment of Clinical and Experimental Pathology, Wrocław Medical University, 50-556 Wrocław, PolandDepartment of Clinical Chemistry, Wrocław Medical University, 50-556 Wrocław, PolandDepartment of Clinical and Experimental Pathology, Wrocław Medical University, 50-556 Wrocław, PolandDepartment of Pharmacology, Wrocław Medical University, 50-345 Wrocław, PolandThe present study investigated whether Rho-associated protein kinase (RhoA/ROCK) signaling pathway inhibitor simvastatin inhibits matrix metalloproteinase 2 (MMP-2) activity in a rat ischemia-reperfusion injury (I/Ri) model by inhibiting the RhoA/ROCK pathway and reducing <i>MMP-2</i> mRNA levels. Isolated rat hearts were subjected to aerobic perfusion or I/Ri control. The effect of simvastatin was assessed in hearts subjected to I/Ri. We determined cardiac mechanical function, the content of RhoA, phosphorylated myosin light chain subunit 1 (phospho-MYL9), troponin I, MMP-2, and <i>MMP-2</i> mRNA in the heart homogenates, as well as MMP-2 activity in heart tissue. We showed that treatment with simvastatin caused improvement in the contractile function of the heart subjected to I/Ri which was accompanied by a decrease of MMP-2 activity in heart tissue along with inhibition of RhoA pathway, expressed in a reduction in both RhoA and its downstream product—phosphorylated myosin light chain (phospho-MYL9) in hearts treated with simvastatin. MMP-2 inactivation is not due to inhibition of <i>MMP-2</i> m-RNA synthesis caused by inhibition of RhoA/ROCK pathway and is due, at least in part, to the direct drug action. The protective effect of simvastatin on systolic function in the acute ischemia-reperfusion model does not appear to be related to reduced MMP-2 activation, but other mechanisms related with the inhibition RhoA/ROCK pathway.https://www.mdpi.com/2218-273X/12/9/1291simvastatinmatrix metalloproteinasesRhoAischemia/reperfusion |
| spellingShingle | Monika Skrzypiec-Spring Agnieszka Sapa-Wojciechowska Alina Rak-Pasikowska Maciej Kaczorowski Iwona Bil-Lula Agnieszka Hałoń Adam Szeląg The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity Biomolecules simvastatin matrix metalloproteinases RhoA ischemia/reperfusion |
| title | The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity |
| title_full | The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity |
| title_fullStr | The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity |
| title_full_unstemmed | The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity |
| title_short | The Protective Effect of Simvastatin on the Systolic Function of the Heart in the Model of Acute Ischemia and Reperfusion Is Due to Inhibition of the RhoA Pathway and Independent of Reduction of MMP-2 Activity |
| title_sort | protective effect of simvastatin on the systolic function of the heart in the model of acute ischemia and reperfusion is due to inhibition of the rhoa pathway and independent of reduction of mmp 2 activity |
| topic | simvastatin matrix metalloproteinases RhoA ischemia/reperfusion |
| url | https://www.mdpi.com/2218-273X/12/9/1291 |
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