Silencing RNA for MMPs May Be Utilized for Cardioprotection

Ischemia/reperfusion (I/R) injury is accompanied by an increase of matrix metalloproteinase 2 (MMP-2) activity, which degrades heart contractile proteins. The aim of the study was to investigate the effect of MMP-2 small interfering RNA (MMP-2 siRNA) administration on I/R heart. Isolated rat hearts...

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Main Authors: Marta Banaszkiewicz, Anna Krzywonos-Zawadzka, Agnieszka Olejnik, Agnieszka Noszczyk-Nowak, Iwona Bil-Lula
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Cardiovascular Therapeutics
Online Access:http://dx.doi.org/10.1155/2022/9729018
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author Marta Banaszkiewicz
Anna Krzywonos-Zawadzka
Agnieszka Olejnik
Agnieszka Noszczyk-Nowak
Iwona Bil-Lula
author_facet Marta Banaszkiewicz
Anna Krzywonos-Zawadzka
Agnieszka Olejnik
Agnieszka Noszczyk-Nowak
Iwona Bil-Lula
author_sort Marta Banaszkiewicz
collection DOAJ
description Ischemia/reperfusion (I/R) injury is accompanied by an increase of matrix metalloproteinase 2 (MMP-2) activity, which degrades heart contractile proteins. The aim of the study was to investigate the effect of MMP-2 small interfering RNA (MMP-2 siRNA) administration on I/R heart. Isolated rat hearts perfused by the Langendorff method were subjected to I/R in the presence or absence of MMP-2 siRNA. The hemodynamic parameters of heart function were monitored. Lactate dehydrogenase (LDH) activity was measured in coronary effluents. Activity and concentration of MMPs in the hearts were measured. Concentration of troponin I (TnI) in coronary effluents was examined as a target for MMP-2 degradation. Recovery of heart mechanical function was reduced after I/R; however, administration of MMP-2 siRNA resulted in restoration of proper mechanical function (p<0.001). LDH activity was decreased after the use of MMP-2 siRNA (p=0.02), providing evidence for reduced cardiac damage. Both MMP-2 and MMP-9 syntheses as well as their activity were inhibited in the I/R hearts after siRNA administration (p<0.05). MMP-2 siRNA administration inhibited TnI release into the coronary effluents (p<0.001). The use of MMP-2 siRNA contributed to the improvement of heart mechanical function and reduction of contractile proteins degradation during I/R; therefore, MMP-2 siRNA may be considered a cardioprotective agent.
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series Cardiovascular Therapeutics
spelling doaj-art-35e7a5abcc134e20aa16e96f8151e9942025-02-03T05:57:23ZengWileyCardiovascular Therapeutics1755-59222022-01-01202210.1155/2022/9729018Silencing RNA for MMPs May Be Utilized for CardioprotectionMarta Banaszkiewicz0Anna Krzywonos-Zawadzka1Agnieszka Olejnik2Agnieszka Noszczyk-Nowak3Iwona Bil-Lula4Division of Clinical Chemistry and Laboratory HematologyDivision of Clinical Chemistry and Laboratory HematologyDivision of Clinical Chemistry and Laboratory HematologyDepartment of Internal Medicine and Clinic of Diseases of HorsesDivision of Clinical Chemistry and Laboratory HematologyIschemia/reperfusion (I/R) injury is accompanied by an increase of matrix metalloproteinase 2 (MMP-2) activity, which degrades heart contractile proteins. The aim of the study was to investigate the effect of MMP-2 small interfering RNA (MMP-2 siRNA) administration on I/R heart. Isolated rat hearts perfused by the Langendorff method were subjected to I/R in the presence or absence of MMP-2 siRNA. The hemodynamic parameters of heart function were monitored. Lactate dehydrogenase (LDH) activity was measured in coronary effluents. Activity and concentration of MMPs in the hearts were measured. Concentration of troponin I (TnI) in coronary effluents was examined as a target for MMP-2 degradation. Recovery of heart mechanical function was reduced after I/R; however, administration of MMP-2 siRNA resulted in restoration of proper mechanical function (p<0.001). LDH activity was decreased after the use of MMP-2 siRNA (p=0.02), providing evidence for reduced cardiac damage. Both MMP-2 and MMP-9 syntheses as well as their activity were inhibited in the I/R hearts after siRNA administration (p<0.05). MMP-2 siRNA administration inhibited TnI release into the coronary effluents (p<0.001). The use of MMP-2 siRNA contributed to the improvement of heart mechanical function and reduction of contractile proteins degradation during I/R; therefore, MMP-2 siRNA may be considered a cardioprotective agent.http://dx.doi.org/10.1155/2022/9729018
spellingShingle Marta Banaszkiewicz
Anna Krzywonos-Zawadzka
Agnieszka Olejnik
Agnieszka Noszczyk-Nowak
Iwona Bil-Lula
Silencing RNA for MMPs May Be Utilized for Cardioprotection
Cardiovascular Therapeutics
title Silencing RNA for MMPs May Be Utilized for Cardioprotection
title_full Silencing RNA for MMPs May Be Utilized for Cardioprotection
title_fullStr Silencing RNA for MMPs May Be Utilized for Cardioprotection
title_full_unstemmed Silencing RNA for MMPs May Be Utilized for Cardioprotection
title_short Silencing RNA for MMPs May Be Utilized for Cardioprotection
title_sort silencing rna for mmps may be utilized for cardioprotection
url http://dx.doi.org/10.1155/2022/9729018
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AT annakrzywonoszawadzka silencingrnaformmpsmaybeutilizedforcardioprotection
AT agnieszkaolejnik silencingrnaformmpsmaybeutilizedforcardioprotection
AT agnieszkanoszczyknowak silencingrnaformmpsmaybeutilizedforcardioprotection
AT iwonabillula silencingrnaformmpsmaybeutilizedforcardioprotection