Dataset Information

MicroRNA-145 Protects against Myocardial Ischemia Reperfusion Injury via CaMKII-Mediated Antiapoptotic and Anti-Inflammatory Pathways.

ABSTRACT: MicroRNA-145 (miR-145) has been shown to play an important role in cardiovascular system disorders; however, the underlying mechanism is not completely understood. The purpose of this study was aimed at elucidating the cardioprotective effects of miR-145 against myocardial ischemia/reperfusion (I/R) injury. We established a rat myocardial I/R model with 45 min left anterior descending coronary artery (LAD) occlusion and 2 h reperfusion. The levels of myocardial enzymes, apoptotic, inflammatory, and oxidative indices were determined. The arrhythmia score was assessed by programmed electrical stimulation (PES). Quantitative real-time PCR and western blot were applied to evaluate the expression levels of miR-145 and related target proteins, respectively. I/R injury decreased the expression of miR-145; however, upregulated miR-145 markedly reduced the elevation of ST segment, decreased corrected QT (QTc) intervals, and attenuated I/R-induced electrophysiological instability. Furthermore, miR-145 suppressed myocardium apoptotic, inflammatory, and oxidative response as well as the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII), ryanodine receptor2 (RyR2 Ser2814), apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinases (JNK), and nuclear translocation of nuclear factor kappa-B (NF-κB) p65. In summary, overexpression of miR-145 alleviates I/R-induced myocardial electrophysiological instability and apoptotic and inflammatory response via inhibition of the CaMKII-mediated ASK1 antiapoptotic pathway and NF-κB p65 anti-inflammatory pathways.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6754948 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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MicroRNA-145 Protects against Myocardial Ischemia Reperfusion Injury via CaMKII-Mediated Antiapoptotic and Anti-Inflammatory Pathways.

Liu Zhebo Z Tao Bo B Fan Suzhen S Pu Yong Y Xia Hao H Xu Lin L

Oxidative medicine and cellular longevity 20190910

MicroRNA-145 (miR-145) has been shown to play an important role in cardiovascular system disorders; however, the underlying mechanism is not completely understood. The purpose of this study was aimed at elucidating the cardioprotective effects of miR-145 against myocardial ischemia/reperfusion (I/R) injury. We established a rat myocardial I/R model with 45 min left anterior descending coronary artery (LAD) occlusion and 2 h reperfusion. The levels of myocardial enzymes, apoptotic, inflammatory, ...[more]

PMID: 31583047

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Project description:Gum Arabic (GA) is a plant exudate with antioxidant and anti-inflammatory effects. GA has shown promise in protection from and treatment of kidney failure, however, its role in the protection of the heart from ischemia and reperfusion (I/R) has not been investigated. This study investigated the antioxidant and anti-inflammatory effects of Gum Arabic (GA) in the protection of the heart against ischemia/reperfusion (I/R) injury. Langendorff-perfused Wistar rat hearts were divided into seven groups. One group which was subjected to I/R with no other treatment served as the control group. The second group was subjected to buffer perfusion with no ischemia (sham group). The third group was perfused with GA in the absence of ischemia (sham + GA). The rest of the hearts were isolated from rats that had been treated with GA for 4 or 2 weeks in the drinking water, or GA that had been infused intravenously 2 h before sacrifice or added to perfusion buffer at reperfusion. Hemodynamics data were digitally computed; infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining and cardiomyocyte injury was assessed by quantifying creatine kinase (CK) and lactate dehydrogenase (LDH) enzymes. The total oxidants (TOS) and antioxidants (TAS), superoxide dismutase (SOD) and pro- and anti-inflammatory cytokines levels were estimated by ELISA. GA treatment for 2 weeks, 4 weeks or 2 hours before sacrifice resulted in a significant (P < 0.05) improvement in cardiac hemodynamics and reduction in infarct size and cardiac enzyme levels compared to respective controls. However, GA administration at the time of reperfusion did not protect the hearts against I/R injury. Furthermore, GA treatment decreased the pro-inflammatory and anti-inflammatory cytokines levels. The levels of TOS in the effluent were significantly decreased (P < 0.05) and SOD levels were significantly (P < 0.05) increased by GA administration. GA protected the heart against I/R injury when administered for 2 or 4 weeks or when infused 2 hours before sacrifice. GA treatment decreased the total oxidants levels, the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 protein levels and increases SOD and anti-inflammatory cytokine IL-10 protein levels.

Project description:Background:Oxidative stress is a major contributor to the onset and development of myocardial ischemia reperfusion injury (MIRI). Sappanone A (SA), a homoisoflavanone extracted from the heartwood of Caesalpinia sappan L., has been demonstrated to possess powerful antioxidant activity. Therefore, this study aimed to determine the protective effect of SA on MIRI and investigate its underlying mechanism. Methods:The rat hearts were isolated and underwent 30-min ischemia, followed by 120-min reperfusion to establish the MIRI model, using the Langendorff method. SA was administrated intraperitoneally into rats 1 h prior to heart isolation. The myocardial infarct size and apoptosis were measured by TTC and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Myocardial enzyme activity, MDA content and the activities of SOD and GSH-Px were detected by colorimetric spectrophotometric method. Reactive oxygen species (ROS) level was detected by DCFH-DA probe. The change in Keap1/Nrf2 signaling pathway was evaluated by Western blotting. Results:SA reduced myocardial infarct size and the release of CK-MB and LDH in a dose-dependent manner. Moreover, SA improved the recovery of cardiac function, inhibited MIRI-induced apoptosis, repressed the production of ROS and MDA, and enhanced the activities of SOD and GSH-Px. Mechanistically, SA downregulated Keap1, induced Nrf2 nuclear accumulation, and enhanced Nrf2 transcriptional activity, subsequently resulting in an increase in the expression of the Nrf2 target genes heme oxygenase-1 and NAD(P)H quinone dehydrogenase 1. Moreover, SA enhanced the phosphorylation of Nfr2, but the enhancement in Nfr2 phosphorylation was abrogated by PKC or PI3K inhibitor. Conclusion:Collectively, it was demonstrated that SA prevents MIRI via coordinating the cellular antioxidant defenses and maintaining the redox balance, by modulation of Nrf2 via the PKC or PI3K pathway. Therefore, SA was a potential therapeutic drug for treating MIRI.

Dataset Information

MicroRNA-145 Protects against Myocardial Ischemia Reperfusion Injury via CaMKII-Mediated Antiapoptotic and Anti-Inflammatory Pathways.

Publications

MicroRNA-145 Protects against Myocardial Ischemia Reperfusion Injury via CaMKII-Mediated Antiapoptotic and Anti-Inflammatory Pathways.

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