Silencing RNA for MMPs May Be Utilized for Cardioprotection. (24th August 2022)

• Record Type: Journal Article
• Authors: Banaszkiewicz, Marta; Krzywonos-Zawadzka, Anna; Olejnik, Agnieszka; Noszczyk-Nowak, Agnieszka; Bil-Lula, Iwona
• Other Names: Xu Baohui Academic Editor.
• Is Part Of: Cardiovascular therapeutics. Volume 2022(2022)
• Publication Date: 2022-08-24
• Subjects: Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular system -- Diseases -- Chemotherapy -- Periodicals; Cardiovascular Agents -- Periodicals; Cardiovascular Diseases -- drug therapy -- Periodicals; Agents cardiovasculaires -- Périodiques; Appareil cardiovasculaire -- Maladies -- Chimiothérapie -- Périodiques; 616.1005
• DOI: 10.1155/2022/9729018
• Languages: English
• ISSNs: 1755-5914

Abstract

Abstract : 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.