ERK1/2-Egr-1 Signaling Pathway-Mediated Protective Effects of Electroacupuncture in a Mouse Model of Myocardial Ischemia-Reperfusion

Early growth response- (Egr-) 1 is an upstream master switch in controlling inflammatory responses following myocardial ischemia-reperfusion (I/R). Activation of extracellular signal-regulated protein kinase-1 and kinase-2 (ERK1/2) signaling is known to upregulate Egr-1. ERK1/2 pathway has been previously shown to mediate the therapeutic action of electroacupucture (EA). Thus, we hypothesized that EA would reduce myocardial I/R injury and inflammatory responses through inhibiting Egr-1 expression via the ERK1/2 pathway. Mice were pretreated with EA, U0126, or combination of EA and U0126 and then underwent 1 h myocardial ischemia and 3 h reperfusion. We investigated that EA significantly attenuated the I/R-induced upregulation of both Egr-1 and phosporylated-ERK1/2 (p-ERK1/2), decreased myocardial inflammatory cytokines including tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β), and reduced the infarct size and the release of cardiac troponin I (cTnI). U0126 treatment also exhibited the same effect as EA on Egr-1 level and subsequent cardioprotective effects. There was no additive effect of cotreatment with EA and U0126 on the expression of Egr-1 and its downstream target genes (TNF-α, IL-1β) or serum cTnI level. Collectively, these observations suggested that EA attenuates myocardial I/R injury, possibly through inhibiting the ERK1/2-Egr-1 signaling pathway and reducing the release of proinflammatory cytokines.

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Protective effects of N(2)‑L‑alanyl‑L‑glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion

Molecular Medicine Reports ◽

10.3892/mmr.2018.8543 ◽

2018 ◽

Cited By ~ 1

Author(s):

Shan Liu ◽

Yang Yang ◽

Yan Qiu Song ◽

Jie Geng ◽

Qing Liang Chen

Keyword(s):

Myocardial Ischemia ◽

Signaling Pathway ◽

Ischemia Reperfusion ◽

Protective Effects ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

Myocardial Ischemia Reperfusion

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Luteolin modulates SERCA2a via Sp1 upregulation to attenuate myocardial ischemia/reperfusion injury in mice

Scientific Reports ◽

10.1038/s41598-020-72325-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ya Hu ◽

Chengmeng Zhang ◽

Hong Zhu ◽

Shuai Wang ◽

Yao Zhou ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Troponin I ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Transcriptional Level ◽

Protective Effects ◽

Myocardial Ischemia Reperfusion Injury ◽

Regulatory Effects ◽

Myocardial Ischemia Reperfusion

Abstract The sarco/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) is responsible for calcium transport during excitation–contraction coupling and is essential for maintaining myocardial systolic/diastolic function and intracellular Ca2+ levels. Therefore, it is important to investigate mechanisms whereby luteolin modulates SERCA2a expression to attenuate myocardial ischemia/reperfusion injury. C57BL/6j mice were randomly divided into eight groups. The expression and activity of SERCA2a was measured to assess interactions between the SERCA2a promoter and the Sp1 transcription factor, and the regulatory effects of luteolin. We used serum LDH release, serum cardiac troponin I level, hemodynamic data, myocardial infarction size and apoptosis-related indices to measure SERCA2a cardio-protective effects of luteolin pretreatment. Sp1 binding to SERCA2a promoter under ischemia/reperfusion conditions in the presence or absence of luteolin was analyzed by chromatin immunoprecipitation. Our experimental results indicated that during myocardial ischemia/reperfusion injury, luteolin pretreatment upregulated the expression levels of SERCA2a and Sp1. Sp1 overexpression enhanced the expression of SERCA2a at the transcriptional level. Luteolin pretreatment reversed the expression of SERCA2a through the increased expression of Sp1. Moreover, we demonstrated that luteolin pretreatment appeared to exert myocardial protective effects by upregulating the transcriptional activity of SERCA2a, via Sp1. In conclusion, during myocardial ischemia/reperfusion, Sp1 appeared to downregulate the expression of SERCA2a. Luteolin pretreatment was shown to improve SERCA2a expression via the upregulation of Sp1 to attenuate myocardial ischemia/reperfusion injury.

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Irbesartan ameliorate inflammatory responses, and apoptosis induced by myocardial ischemia/reperfusion in male rats

American Journal of BioMedicine ◽

10.18081/2333-5106/019-2/138-150 ◽

2019 ◽

Vol 7 (2) ◽

pp. 138-150

Author(s):

Najah R. Hadi ◽

Fadhil G. Al-Amran

Keyword(s):

Myocardial Ischemia ◽

Troponin I ◽

Inflammatory Responses ◽

Ischemia Reperfusion ◽

Cardiac Injury ◽

Male Rats ◽

Control Group ◽

Inflammatory Reactions ◽

Tnf Α ◽

Myocardial Ischemia Reperfusion

Myocardial ischemia–reperfusion (I-R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. This study was undertaken to investigate the potential role of Irbesartan in amelioration of myocardial I/R injury induced by ligation of coronary artery (LAD) in a rat model. We are pretreated the animals with Irbesartan 3mg/kg i.p. 30 minutes before ligation of LAD. At the end of experiment (2 h of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I (cTn-I). Compared with the sham group, levels of myocardial TNF-α, IL-1β, IL-6, MCP-1, MIP-1 alpha, and plasma cTn-I were increased (P<0.05). Histologically, all rats in control group showed significant cardiac injury after I-R. Furthermore, rats in control group showed significant apoptosis. Irbesartan significantly counteract the increased in myocardium level of TNF-α, IL-1B, IL-6, MCP-1, MIP-1 alpha, plasma cTn-I and apoptotosis (P<0.05). Histological analysis revealed that Irbesartan markedly reduced the severity of heart injury in the rats underwent LAD ligation procedure. We concluded that Irbesartan may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which induced by I/R injury.

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Expression Profiles and Ontology Analysis of Circular RNAs in a Mouse Model of Myocardial Ischemia/Reperfusion Injury

BioMed Research International ◽

10.1155/2020/2346369 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Zhaoqing Sun ◽

Tongtong Yu ◽

Yundi Jiao ◽

Dongxu He ◽

Jiake Wu ◽

...

Keyword(s):

Myocardial Ischemia ◽

Signaling Pathway ◽

High Throughput Sequencing ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Expression Profiles ◽

Ischemia Reperfusion ◽

Adherens Junction ◽

Circular Rnas ◽

Myocardial Ischemia Reperfusion

Circular RNAs (circRNAs) play important roles in cellular physiology. The association between circRNAs and myocardial ischemia/reperfusion (I/R) injury remains largely unknown. The aim of this study was to test the effects of myocardial I/R circRNA expression and explore the potential roles of these circRNAs. CircRNAs were screened by high-throughput sequencing, and the expression of dysregulated circRNAs was further validated using quantitative real-time polymerase chain reaction. Nineteen upregulated and 20 downregulated circRNAs were identified. Gene Ontology analysis indicated that the dysregulated transcripts were associated with fundamental pathophysiologic processes. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed significant changes in adherens junction, the HIF-1 signaling pathway, the cell cycle, and the FoxO signaling pathway which have a close relationship with myocardial I/R injury. The circRNA-miRNA analysis demonstrated the broad potential of the differentially expressed circRNAs to regulate target genes by acting on the miRNAs. This study provides a foundation for understanding the roles and mechanisms of circRNAs in myocardial I/R injury.

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