scholarly journals Sevoflurane Pre-conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation of p38 and ERK

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dina Xie ◽  
Jianli Zhao ◽  
Rui Guo ◽  
Liyuan Jiao ◽  
Yanqing Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inhibitory Effect ◽  
Normal Diet ◽  
Dominant Negative ◽  
Ampk Signaling ◽  
Clinical Scenarios ◽  
Myocardial Ischemia Reperfusion

AbstractDiabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms. Normal diet (ND) and high-fat diet (HFD)-induced DM mice were randomized into control and SF-PreCon (3 cycles of 15-minute period exposures to 2% sevoflurane) groups before MI/R. SF-PreCon markedly reduced MI/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and ±Dp/dt), decreased infarct size, and decreased apoptosis. To determine the relevant role of AMPK, the effect of SF-PreCon was determined in cardiac-specific AMPKα2 dominant negative expressing mice (AMPK-DN). SF-PreCon decreased MI/R injury in AMPK-DN mice. To explore the molecular mechanisms responsible for SF-PreCon mediated cardioprotection in DM mice, cell survival molecules were screened. Interestingly, in ND mice, SF-PreCon significantly reduced MI/R-induced activation of p38, a pro-death MAPK, without altering ERK and JNK. In DM and AMPK-DN mice, the inhibitory effect of SF-PreCon upon p38 activation was significantly blunted. However, SF-PreCon significantly increased phosphorylation of ERK1/2, a pro-survival MAPK in DM and AMPK-DN mice. We demonstrate that SF-PreCon protects the heart via AMPK-dependent inhibition of pro-death MAPK in ND mice. However, SF-PreCon exerts cardioprotective action via AMPK-independent activation of a pro-survival MAPK member in DM mice. SF-PreCon may be beneficial compared to conventional PreCon in diabetes or clinical scenarios in which AMPK signaling is impaired.

Abstract 11302: Sevoflurane Pre-Conditioning Effectively Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury via Differential Regulation of p38 and ERK

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jianli Zhao ◽  
Jingjing Li ◽  
Rui Li ◽  
Liyuan Jiao ◽  
Yanqing Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inhibitory Effect ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Ampk Signaling ◽  
Myocardial Ischemia Reperfusion

Diabetes (DB) significantly exacerbates myocardial ischemia/reperfusion (MI/R) injury. Unfortunately, conventional pre-conditioning (PreCon) provides diminished cardioprotection during DB, due partially to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon by inhaled anesthetic sevoflurane (SF-PreCon) remains protective in DB, and if so, to dissect the involved mechanisms. Non-diabetic (ND) or high-fat diet-induced DB mice were subjected to MI/R and randomized into control and SF-PreCon (3 cycles of 15 minute-exposures to 2% sevoflurane prior to MI) groups. As expected, SF-PreCon significantly reduced MI/R injury in ND mice. Importantly, SF-PreCon also significantly reduced MI/R injury in DB mice, as evidenced by reduced apoptosis (-23.1±1.6, P<0.01), decreased infarct size (-21.2±2.3%, P<0.01), and augmented cardiac function (+24±3.0%, P<0.01). To determine the role of AMPK in SF-PreCon-mediated cardioprotection, the effect of SF-PreCon upon MI/R injury was determined in cardiac specific AMPKα2 dominant negative overexpression mice (AMPK-DN). We demonstrate SF-PreCon remained cardioprotective in AMPK-DN mice. To explore the responsible molecular mechanisms, multiple cell-survival signaling molecules were screened. Interestingly, SF-PreCon differentially regulated mitogen-activated protein kinase (MAPK) family members in the MI/R heart. In ND mice, SF-PreCon dramatically reduced (-81±7.2%) MI/R-induced activation of p38, a pro-death MAPK, without significantly altering ERK and JNK. In DB and AMPK-DN mice, the inhibitory effect of SF-PreCon upon p38 activation was significantly blunted (DB: -8±2.1%) or virtually abolished (AMPK-DN). However, SF-PreCon significantly increased (P<0.05) phosphorylation of ERK1/2, a pro-survival MAPK. Collectively, we demonstrate SF-PreCon protected the heart via AMPK-dependent inhibition of pro-death MAPK in ND mice. However, SF-PreCon exerts its cardioprotective actions via AMPK-independent activation of pro-survival MAPK in DB mice. These results suggest SF-PreCon may be a superior intervention over conventional PreCon in DB patients, where AMPK signaling is impaired.

Insight into long noncoding RNA–miRNA–mRNA axes in myocardial ischemia-reperfusion injury: the implications for mechanism and therapy

Epigenomics ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 1733-1748 ◽  
Author(s):  
Wei Xiong ◽  
Yan Qu ◽  
Hongmei Chen ◽  
Jinqiao Qian
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Noncoding Rnas ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Insight Into

Emerging evidence has demonstrated that regulatory noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and miRNAs, play crucial roles in the initiation and progress of myocardial ischemia-reperfusion injury (MIRI), which is associated with autophagy, apoptosis and necrosis of cardiomyocytes, as well as oxidative stress, inflammation and mitochondrial dysfunction. LncRNAs serve as a precursor or host of miRNAs and directly/indirectly affecting miRNAs via competitive binding or sponge effects. Simultaneously, miRNAs post-transcriptionally regulate the expression of genes by targeting various mRNA sequences due to their imperfect pairing with mRNAs. This review summarizes the potential regulatory role of lncRNA–miRNA–mRNA axes in MIRI and related molecular mechanisms of cardiac disorders, also provides insight into the potential therapies for MIRI-induced diseases.

scholarly journals Rno-microRNA-30c-5p promotes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and targeting SIRT1

2020 ◽  
Author(s):  
Jianfeng Chen ◽  
Mingming Zhang ◽  
Shouyan Zhang ◽  
Junlong Wu ◽  
Shufeng Xue
Keyword(s):  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sirtuin 1 ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Cells ◽  
Myocardial Ischemia Reperfusion

Abstract Background: This study aimed to investigate the regulatory effect of rno-microRNA-30c-5p (rno-miR-30c-5p) on myocardial ischemia reperfusion (IR) injury in rats and the underlying molecular mechanisms.Methods: A rat model of myocardial IR injury was established. The infarct size was detected by 2,3,5-triphenyltetrazolium chloride staining. The pathologic changes of myocardial tissues were detected by hematoxylin-eosin staining. The apoptosis of myocardial cells was measured by TUNEL staining and flow cytometry. The mRNA expression of rno-miR-30c-5p and Sirtuin 1 (SIRT1) was detected by quantitative real-time PCR. The levels of IL-1β, IL-6 and TNF-α were detected by enzyme linked immunosorbent assay. The protein expression of Bax, Bcl-2, caspase-3, p-IκBα, IκBα, p-NF-κB p65, NF-κB p65 and SIRT1 was detected by Western blot. The interaction between rno-miR-30c-5p and SIRT1 was predicted by TargetScan, and further identified by dual luciferase reporter gene and RNA immunoprecipitation assay.Results: The myocardial IR injury model was successfully established in rats. IR induced the myocardial injury in rats and increased the expression of rno-miR-30c-5p. Overexpression of rno-miR-30c-5p enhanced the inflammation, promoted the apoptosis, and activated NF-κB pathway in IR myocardial cells. SIRT1 was the target gene of rno-miR-30c-5p. Silencing of SIRT1 reversed the effects of rno-miR-30c-5p inhibitor on the apoptosis and NF-κB pathway in IR myocardial cells.Conclusions: Rno-miR-30c-5p promoted the myocardial IR injury in rats through activating NF-κB pathway and down-regulating SIRT1.

scholarly journals The Emerging Role of Thioredoxin-Interacting Protein in Myocardial Ischemia/Reperfusion Injury

2016 ◽  
Vol 22 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Bing F. Wang ◽  
Jun Yoshioka
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Interacting Protein ◽  
Glucose Transporter 1 ◽  
Thioredoxin Interacting Protein ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia/reperfusion injury represents a major threat to human health and contributes to adverse cardiovascular outcomes worldwide. Despite the identification of numerous molecular mechanisms, understanding of the complex pathophysiology of this clinical syndrome remains incomplete. Thioredoxin-interacting protein (Txnip) has been of great interest in the past decade since it has been reported to be a critical regulator in human diseases with several important cellular functions. Thioredoxin-interacting protein binds to and inhibits thioredoxin, a redox protein that neutralizes reactive oxygen species (ROS), and through its interaction with thioredoxin, Txnip sensitizes cardiomyocytes to ROS-induced apoptosis. Interestingly, evidence from recent studies also suggests that some of the effects of Txnip may be unrelated to changes in thioredoxin activity. These pleiotropic effects of Txnip are mediated by interactions with other signaling molecules, such as nod-like receptor pyrin domain-containing 3 inflammasome and glucose transporter 1. Indeed, Txnip has been implicated in the regulation of inflammatory response and glucose homeostasis during myocardial ischemia/reperfusion injury. This review attempts to make the case that in addition to interacting with thioredoxin, Txnip contributes to some of the pathological consequences of myocardial ischemia and infarction through endogenous signals in multiple molecular mechanisms.

scholarly journals Non-coding RNAs modulate autophagy in myocardial ischemia-reperfusion injury: a systematic review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fuwen Huang ◽  
Jingting Mai ◽  
Jingwei Chen ◽  
Yinying He ◽  
Xiaojun Chen
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Circular Rnas ◽  
Non Coding Rnas ◽  
Myocardial Ischemia Reperfusion

AbstractThe myocardial infarction is the main cause of morbidity and mortality in cardiovascular diseases around the world. Although the timely and complete reperfusion via Percutaneous Coronary Intervention (PCI) or thrombolysis have distinctly decreased the mortality of myocardial infarction, reperfusion itself may lead to supererogatory irreversible myocardial injury and heart function disorders, namely ischemia-reperfusion (I/R) injury. Extensive studies have indicated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play important roles in the progress of myocardial I/R injury, which is closely correlative with cardiomyocytes autophagy. Moreover, autophagy plays an important role in maintaining homeostasis and protecting cells in the myocardial ischemia reperfusion and cardiomyocyte hypoxia-reoxygenation (H/R) progress. In this review, we first introduced the biogenesis and functions of ncRNAs, and subsequently summarized the roles and relevant molecular mechanisms of ncRNAs regulating autophagy in myocardial I/R injury. We hope that this review in addition to develop a better understanding of the physiological and pathological roles of ncRNAs, can also lay a foundation for the therapies of myocardial I/R injury, and even for other related cardiovascular diseases.

Sign in / Sign up

Export Citation Format

Share Document