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 (Author), Anna Krzywonos-Zawadzka (Author), Agnieszka Olejnik (Author), Agnieszka Noszczyk-Nowak (Author), Iwona Bil-Lula (Author)
Format: Book
Published: Hindawi-Wiley, 2022-01-01T00:00:00Z.
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Summary: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.
Item Description:1755-5922
10.1155/2022/9729018