scholarly journals Effect of eNOS on Ischemic Postconditioning-Induced Autophagy against Ischemia/Reperfusion Injury in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jun Shao ◽  
Chen Miao ◽  
Zhi Geng ◽  
Maohong Gu ◽  
Yanhu Wu ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Ischemic Postconditioning ◽  
Coronary Artery Ligation ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
H9c2 Cells

Autophagy is involved in the development of numerous illnesses, including ischemia/reperfusion (I/R). Endothelial nitric oxide synthase (eNOS) participates in the protective effects of ischemic postconditioning (IPostC). However, it remains unclear whether eNOS-mediated autophagy serves as a critical role in IPostC in the hearts of mice, in protecting against I/R injury. In the present study, the hearts of mice with left anterior descending coronary artery ligation were studied as I/R models. H9c2 cells underwent exposure to hypoxia/reoxygenation (H/R) and were examined as in vitro model. IPostC reduced mice myocardial infarct size and improved the structure of the heart. IPostC increased the formation of autophagosomes and increased the phosphorylation of eNOS and adenosine monophosphate-activated protein kinase (AMPK). Autophagy and eNOS inhibition suppressed the cardioprotective effects of IPostC. AMPK or eNOS inhibition abolished the improvement effect of IPostC on autophagy. AMPK inhibition decreased eNOS phosphorylation in the heart. Additionally, H9c2 cells suffering hypoxia were used as in vitro model. Autophagy or eNOS inhibition abolished the protective effects of hypoxic postconditioning (HPostC) against H/R injury. AMPK and eNOS inhibition/knockout decreased autophagic activity in the HPostC group. These results indicated that IPostC protects the heart against I/R injury, partially via promoting AMPK/eNOS-mediated autophagy.

Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning

2008 ◽  
Vol 295 (3) ◽  
pp. H1330-H1340 ◽  
Author(s):  
Qian Chen Yong ◽  
Shiau Wei Lee ◽  
Chun Shin Foo ◽  
Kay Li Neo ◽  
Xin Chen ◽  
...  
Keyword(s):  
Hydrogen Sulphide ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Early Period ◽  
Ischemic Postconditioning ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Rat Hearts ◽  
Underlying Mechanisms

The present study aimed to investigate the role of hydrogen sulphide (H2S) in the cardioprotection induced by ischemic postconditioning and to examine the underlying mechanisms. Cardiodynamics and myocardial infarction were measured in isolated rat hearts. Postconditioning with six episodes of 10-s ischemia (IPostC) significantly improved cardiodynamic function, which was attenuated by the blockade of endogenous H2S production with d-l-propargylglycine. Moreover, IPostC significantly stimulated H2S synthesis enzyme activity during the early period of reperfusion. However, d-l-propargylglycine only attenuated the IPostC-induced activation of PKC-α and PKC-ε but not that of PKC-δ, Akt, and endothelial nitric oxide synthase (eNOS). These data suggest that endogenous H2S contributes partially to the cardioprotection of IPostC via stimulating PKC-α and PKC-ε. Postconditioning with six episodes of a 10-s infusion of NaHS (SPostC) or 2 min continuous NaHS infusion (SPostC2) stimulated activities of Akt and PKC, improved the cardiodynamic performances, and reduced myocardial infarct size. The blockade of Akt with LY-294002 (15 μM) or PKC with chelerythrine (10 μM) abolished the cardioprotection induced by H2S postconditioning. SPostC2, but not SPostC, also additionally stimulated eNOS. We conclude that endogenous H2S contributes to IPostC-induced cardioprotection. H2S postconditioning confers the protective effects against ischemia-reperfusion injury through the activation of Akt, PKC, and eNOS pathways.

scholarly journals Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Hai-Jing Sun ◽  
Yan Lu ◽  
Hao-Wei Wang ◽  
Hao Zhang ◽  
Shuang-Ran Wang ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Ischemia Reperfusion Injury ◽  
Culture Media ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
In Vivo Model ◽  
Myocardial Infarct Size ◽  
Cb2 Receptor

Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS. The reductions of myocardial infarct size in vivo and cardiomyocyte apoptosis and death in vitro were accompanied with attenuations of oxidative injuries manifested as decreased reactive oxygen species (ROS), malonaldehyde (MDA), and MPO (myeloperoxidase) and increased superoxide dismutase (SOD) production. These effects were mimicked by either URB597, a selective endocannabinoids degradation inhibitor, or VDM11, a selective endocannabinoids reuptake inhibitor. In vivo study further validated that the cardioprotective and antioxidative effects of propofol were reversed by selective CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251. We concluded that enhancing endogenous endocannabinoid release and subsequent activation of CB2 receptor signaling represent a major mechanism whereby propofol conditioning confers antioxidative and cardioprotective effects against myocardial I/R injury.

scholarly journals Protective Effect of Peroxisome Proliferator-Activated ReceptorαActivation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jong Wook Song ◽  
Hyo Jung Kim ◽  
Hyelin Lee ◽  
Jae-woo Kim ◽  
Young-Lan Kwak
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Uncoupling Protein ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Myocardial Infarct Size ◽  
Ros Production ◽  
H9c2 Cells ◽  
Ucp3 Expression ◽  
Hypoxia Reoxygenation

Activation of peroxisome proliferator-activated receptorα(PPARα) confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARαactivation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP). Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARαligand, or vehicle. WY-14643 increased UCP3 expressionin vivo. Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%,P<0.05). During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10,P<0.05). H9c2 cells were incubated for 24 h with WY-14643 or vehicle. WY-14643 increased UCP3 expression in H9c2 cells. WY-14643 decreased hypoxia-stimulated ROS production. Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells. Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation. In summary, administration of PPARαagonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia. PPARαactivation conferred cytoprotective effect against hypoxia-reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.

scholarly journals Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 667
Author(s):  
José Lillo-Moya ◽  
Catalina Rojas-Solé ◽  
Diego Muñoz-Salamanca ◽  
Emiliano Panieri ◽  
Luciano Saso ◽  
...  
Keyword(s):  
Blood Flow ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Ischemic Heart ◽  
Myocardial Infarct Size

Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention. This treatment is the gold standard therapy to restore blood flow, but paradoxically it can also induce tissue injury. A number of different studies in animal models of acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up to 50% of the final myocardial infarct size. Oxidative stress plays a critical role in the pathological process. Iron is an essential mineral required for a variety of vital biological functions but also has potentially toxic effects. A detrimental process induced by free iron is ferroptosis, a non-apoptotic type of programmed cell death. Accordingly, efforts to prevent ferroptosis in pathological settings have focused on the use of radical trapping antioxidants (RTAs), such as liproxstatin-1 (Lip-1). Hence, it is necessary to develop novel strategies to prevent cardiac IRI, thus improving the clinical outcome in patients with ischemic heart disease. The present review analyses the role of ferroptosis inhibition to prevent heart IRI, with special reference to Lip-1 as a promising drug in this clinicopathological context.

Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs

2006 ◽  
Vol 290 (3) ◽  
pp. H1011-H1018 ◽  
Author(s):  
Lisa M. Schwartz ◽  
Claudia J. Lagranha
Keyword(s):  
Treatment Group ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Ischemic Postconditioning ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Early Reperfusion ◽  
Occlusion Period

Transient episodes of ischemic preconditioning (PC) render myocardium protected against subsequent lethal injury after ischemia and reperfusion. Recent studies indicate that application of short, repetitive ischemia only during the onset of reperfusion after the lethal ischemic event may obtain equivalent protection. We assessed whether such ischemic postconditioning (Postcon) is cardioprotective in pigs by limiting lethal injury. Pentobarbital sodium-anesthetized, open-chest pigs underwent 30 min of complete occlusion of the left anterior descending coronary artery and 3-h reflow. PC was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. Postcon was elicited by three cycles of 30-s reperfusion, followed by 30-s reocclusion, after the 30-min occlusion period and before the 3-h reflow. Infarct size (%area-at-risk using triphenyltetrazolium chloride macrochemistry; means ± SE) after 30 min of ischemia was 26.5 ± 5.2% ( n = 7 hearts/treatment group). PC markedly limited myocardial infarct size (2.8 ± 1.2%, n = 7 hearts/treatment group, P < 0.05 vs. controls). However, Postcon had no effect on infarct size (37.8 ± 5.1%, n = 7 hearts/treatment group). Within the subendocardium, Postcon increased phosphorylation of Akt (74 ± 12%) and ERK1/2 (56 ± 10%) compared with control hearts subjected only to 30-min occlusion and 15-min reperfusion ( P ≤ 0.05), and these changes were not different from the response triggered by PC ( n = 5 hearts/treatment group). Phosphorylation of downstream p70S6K was also equivalent in PC and Postcon groups. These data do not support the hypothesis that application of 30-s cycles of repetitive ischemia during reperfusion exerts a protective effect on pig hearts subjected to lethal ischemia, but this is not due to a failure to phosphorylate ERK and Akt during early reperfusion.

scholarly journals Influence of ramiprilat and losartan on ischemia reperfusion injury in rat hearts

2011 ◽  
Vol 13 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Fatemeh Safari ◽  
Sohrab Hajizadeh ◽  
Shahnaz Shekarforoush ◽  
Gholamreza Bayat ◽  
Mohsen Foadoddini ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Saline Group ◽  
Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Dependent Manner ◽  
Protective Effects

Hypothesis/introduction: Our aim was to investigate whether a non-hypotensive dose of ramiprilat and losartan has myocardial protective effects during myocardial ischemia/reperfusion in vivo. Materials and methods: Three groups of rats were given 10 mg/kg per day of losartan for one (L-1W), four (L-4W) or 10 (L-10W) weeks. Another three groups were given 50 µg/kg per day of ramiprilat for one (R-1W), four (R-4W) or 10 (R-10W) weeks. The animals underwent 30 min of left anterior descending artery occlusion and subsequent reperfusion for 120 min. Results: Myocardial infarct size (IS) was reduced in R-1W (28.4 ± 6.3%, p < 0.001), R-4W (27.8 ± 7.4, p < 0.001), L-4W (31.8 ± 6%, p < 0.05) and L-10W (25.3 ± 5.7, p < 0.001) groups compared with a saline group (48.3 ± 7.8%). A significant reduction in the number of ventricular ectopic beats (VEBs) was noted in groups R-1W (209 ± 41, p < 0.01), R-4W (176 ± 39, p < 0.01), L-4W (215 ± 52, p < 0.05) and L-10W (191 ± 61, p < 0.01 vs. saline 329 ± 48). The incidence of irreversible ventricular fibrillation (VF) and mortality were decreased significantly only in L-10W group. There were no significant decreases in episodes of VT, the incidence of irreversible VF and mortality in all of the groups treated with ramiprilat. Conclusion: These data indicate that losartan and ramiprilat protect the heart against ischemia/reperfusion injury independently of their hemodynamic effects but in a time-dependent manner.

Sirtuin 1 activated by SRT1460 protects against myocardial ischemia/reperfusion injury

2021 ◽  
pp. 1-11
Author(s):  
Shanjun Zhao ◽  
Lei Yu
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Sirtuin 1 ◽  
In Vitro Assays ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Infarct Area ◽  
Myocardial Ischemia Reperfusion

BACKGROUND: Ischemia reperfusion usually results in certain degree of damage to the myocardium, which is called myocardial ischemia/reperfusion (I/R) injury. OBJECTIVE: Previous studies have found that Sirt1 plays a critical role in I/R injury by protecting cardiac function. SRT1460 is the activator for Sirt1 that participates in the regulation of various diseases. However, whether SRT1460 has any effects on myocardial I/R injury needs further study. METHODS: The I/R rat model and H/R H9C2 model were established to simulate myocardial I/R injury. The infarct area of the rat heart was examined through TTC staining. The EF and FS of rats were detected through echocardiography. The levels of CK-MB, LDH, MDA, SOD and CK in cardiac tissues, serum or H9C2 cells were measured using commercial kits. Cell viability was assessed through MTT assay. Apoptosis was determined through flow cytometry analysis. Sirt1 expression was measured through western blot. RESULTS: Our work found that SRT1460 reduced the infarct area of the heart induced by myocardial I/R injury. In addition, SRT1460 was confirmed to ameliorate cardiac dysfunction induced by myocardial I/R injury. Further exploration discovered that SRT1460 weakened oxidative stress induced by myocardial I/R injury. Findings from in vitro assays demonstrated that SRT1460 relieved injury of H/R-treated H9C2 cells. Finally, rescue assays proved that Sirt1 knockdown reversed the protective effects of SRT1460 on the injury of H/R-treated H9C2 cells. CONCLUSION: Sirt1 activated by SRT1460 protected against myocardial I/R injury. This discovery may offer new sights on the treatment of myocardial I/R injury.

scholarly journals Luteolin Modulates SERCA2a Leading to Attenuation of Myocardial Ischemia/ Reperfusion Injury via Sumoylation at Lysine 585 in Mice

2018 ◽  
Vol 45 (3) ◽  
pp. 883-898 ◽  
Author(s):  
Yinping Du ◽  
Ping Liu ◽  
Tongda Xu ◽  
Defeng Pan ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background/Aims: The myocardial sarcoplasmic reticulum calcium ATPase (SERCA2a) is a pivotal pump responsible for calcium cycling in cardiomyocytes. The present study investigated the effect of luteolin (Lut) on restoring SERCA2a protein level and stability reduced by myocardial ischemia/reperfusion (I/R) injury. We verified a hypothesis that Lut protected against myocardial I/R injury by regulating SERCA2a SUMOylation. Methods: The hemodynamic data, myocardial infarct size of intact hearts, apoptotic analysis, mitochondrial membrane potential (ΔΨm), the level of SERCA2a SUMOylation, and the activity and expression of SERCA2a were examined in vivo and in vitro to clarify the cardioprotective effects of Lut after SUMO1 was knocked down or over-expressed. The putative SUMO conjugation sites in mouse SERCA2a were investigated as the possible regulatory mechanism of Lut. Results: Initially, we found that Lut reversed the SUMOylation and stability of SERCA2a as well as the expression of SUMO1, which were reduced by I/R injury in vitro. Furthermore, Lut increased the expression and activity of SERCA2a partly through SUMO1, thus improving ΔΨm and reducing apoptotic cells in vitro and promoting the recovery of heart function and reducing infarct size in vivo. We also demonstrated that SUMO acceptor sites in mouse SERCA2a involving lysine 585, 480 and 571. Among the three acceptor sites, Lut enhanced SERCA2a stability via lysine 585. Conclusions: Our results suggest that Lut regulates SERCA2a through SUMOylation at lysine 585 to attenuate myocardial I/R injury.

scholarly journals MiR-31 Downregulation Protects Against Cardiac Ischemia/Reperfusion Injury by Targeting Protein Kinase C Epsilon (PKCe) Directly

2015 ◽  
Vol 36 (1) ◽  
pp. 179-190 ◽  
Author(s):  
Yongyi Wang ◽  
Min Men ◽  
Wengang Yang ◽  
Hui Zheng ◽  
Song Xue
Keyword(s):  
Reperfusion Injury ◽  
Target Gene ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Cardiac Ischemia ◽  
Cardioprotective Effect ◽  
Myocardial Infarct Size

Background: Various miRNAs have been shown to participate in cardiac ischemia/reperfusion injury (I/R). miR-31 was identified as the most strikingly upregulated miRNA after acute myocardial infarction; therefore, the underlying role and mechanism of miR-31 in cardiac I/R was investigated. Methods: miR-31 expression was detected after cardiac I/R in mice. The cardioprotective effect of miR-31 downregulation was assessed in vitro and in vivo. The functional target gene and its downstream molecule were determined. Results: miR-31 expression increased after I/R. miR-31 downregulation increased cell viability and SOD activity and decreased LDH activity and MDA content in vitro. Additionally, miR-31 downregulation alleviated myocardial infarct size in vivo. PKCe was identified as the functional target gene of miR-31, and NFκB was identified as its downstream molecule that was involved in the miR-31-mediated cardioprotective effect. Conclusion: miR-31 expression increased throughout the cardiac I/R process, and miR-31 downregulation induced a cardioprotective effect via a miR-31/PKCe/NFκB-dependent pathway.

scholarly journals Validation of efficacy and mechanism of Sanwei-Tanxiang powder in improving myocardial ischemia reperfusion injuries

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Hui Sun ◽  
Ren Bu ◽  
Yue-Wu Wang ◽  
Yu-Chong Hu ◽  
Xu-Mei Wang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ex Vivo ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Tibetan Medicine ◽  
Myocardial Infarct Size ◽  
Protective Effects

AbstractSanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX’s cardioprotection effect.

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