Interleukin-6 mediates exercise preconditioning against myocardial ischemia reperfusion injury

2015 ◽  
Vol 308 (11) ◽  
pp. H1423-H1433 ◽  
Author(s):  
Graham Ripley McGinnis ◽  
Christopher Ballmann ◽  
Bridget Peters ◽  
Gayani Nanayakkara ◽  
Michael Roberts ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Exercise Session ◽  
Sham Operation ◽  
Myocardial Preconditioning ◽  
Exercise Preconditioning ◽  
Myocardial Ischemia Reperfusion ◽  
Exercise Induced ◽  
Protective Signaling

Interleukin-6 (IL-6) is a pleiotropic cytokine that protects against cardiac ischemia-reperfusion (I/R) injury following pharmacological and ischemic preconditioning (IPC), but the affiliated role in exercise preconditioning is unknown. Our study purpose was to characterize exercise-induced IL-6 cardiac signaling ( aim 1) and evaluate myocardial preconditioning ( aim 2). In aim 1, C57 and IL-6−/− mice underwent 3 days of treadmill exercise for 60 min/day at 18 m/min. Serum, gastrocnemius, and heart were collected preexercise, immediately postxercise, and 30 and 60 min following the final exercise session and analyzed for indexes of IL-6 signaling. For aim 2, a separate cohort of exercise-preconditioned (C57 EX and IL-6−/− EX) and sedentary (C57 SED and IL-6−/− SED) mice received surgical I/R injury (30 min I, 120 min R) or a time-matched sham operation. Ischemic and perfused tissues were examined for necrosis, apoptosis, and autophagy. In aim 1, serum IL-6 and IL-6 receptor (IL-6R), gastrocnemius, and myocardial IL-6R were increased following exercise in C57 mice only. Phosphorylated (p) signal transducer and activator of transcription 3 was increased in gastrocnemius and heart in C57 and IL-6−/− mice postexercise, whereas myocardial iNOS and cyclooxygenase-2 were unchanged in the exercised myocardium. Exercise protected C57 EX mice against I/R-induced arrhythmias and necrosis, whereas arrhythmia score and infarct outcomes were higher in C57 SED, IL-6−/− SED, and IL-6−/− EX mice compared with SH. C57 EX mice expressed increased p-p44/42 MAPK (Thr202/Tyr204) and p-p38 MAPK (Thr180/Tyr182) compared with IL-6−/− EX mice, suggesting pathway involvement in exercise preconditioning. Findings indicate exercise exerts cardioprotection via IL-6 and strongly implicates protective signaling originating from the exercised skeletal muscle.

scholarly journals Dexmedetomidine Attenuates Myocardial Ischemia-Reperfusion Injury in Diabetes Mellitus by Inhibiting Endoplasmic Reticulum Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jinjie Li ◽  
Ying Zhao ◽  
Nan Zhou ◽  
Longyun Li ◽  
Kai Li
Keyword(s):  
Endoplasmic Reticulum ◽  
Myocardial Ischemia ◽  
Endoplasmic Reticulum Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sham Operation ◽  
Sham Operation Group ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Objective. With the increasing incidence of diabetes mellitus (DM) combined with myocardial ischemia, how to reduce myocardial ischemia-reperfusion injury in DM patients has become a major problem faced by clinicians. We investigated the therapeutic effects of dexmedetomidine (DEX) on myocardial ischemia-reperfusion injury in DM rats and its effect on endoplasmic reticulum stress. Methods. SD rats with SPF grade were randomly divided into 6 groups: non-DM rats were divided into the sham operation group (NDM-S group), ischemia-reperfusion group (NDM-IR group), and dexmedetomidine group (NDM-DEX group); DM rats were divided into the diabetic sham operation group (DM-S group), diabetes-reperfusion group (DM-IR group), and diabetes-dexmedetomidine (DM-DEX) group, with 10 rats in each group. Then the effects of DEX on the changes of CK-MB and cTnT levels were examined. The effects of myocardial pathological damage and myocardial infarct size were detected. The apoptosis of cardiomyocytes was detected. The apoptosis of heart tissue cells was also tested through the expressions of cleaved caspase-3, Bcl-2, and Bax proteins. The expression of endoplasmic reticulum stress-related proteins GRP78, CHOP, ERO1α, ERO1β, and PDI was examined. The hypoxia/reoxygenation (H/R) injury cell model was established, the effects of DEX, DEX+ ERS agonist on cell apoptosis was also detected. Results. The myocardial damage of DM-IR was more severe than that of NDM-IR rats. DEX could reduce the expression of CK-MB and cTnT, reduce pathological damage, and reduce scar formation and improve fibrosis. DEX can reduce the expression of GRP78, CHOP, ERO1α, ERO1β, and PDI proteins in vivo and in vitro. And the effect of DEX on cell apoptosis could be blocked by ERS agonist. Conclusion. DEX attenuates myocardial ischemia-reperfusion injury in DM rats and H/R injury cell, which is associated with the reduction of ERS-induced cardiomyocyte apoptosis.

scholarly journals Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yi Tian ◽  
Haobo Li ◽  
Peiyu Liu ◽  
Jun-mei Xu ◽  
Michael G. Irwin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Volatile Anesthetic ◽  
Myocardial Inflammation ◽  
Sham Operation ◽  
Replacement Surgery ◽  
Myocardial Apoptosis ◽  
Myocardial Ischemia Reperfusion

Background.Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury.Methods and Results.Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress.Conclusion.A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation.

Abstract 099: Exercise-Induced Cardioprotection Against Ischemia-Reperfusion Injury Is Abolished by Opioid System Blockage Using an In Vitro Rat Model

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Juliana P Borges ◽  
Lorena S Paes ◽  
Eduardo V Tibiriçá ◽  
Marcos A Lessa
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Maximal Oxygen Consumption ◽  
Opioid System ◽  
Exercise Session ◽  
Male Wistar Rats ◽  
Exercise Induced ◽  
Developed Pressure ◽  
Naloxone Treatment

Introduction: A single exercise session releases opioid peptides considered to be associated to cardioprotection. However, the link between exercise-induced cardioprotection and the opioid system remains unclear. Therefore, the study aims to investigate the involvement of opioid receptors in exercise-induced cardioprotection in rats submitted to myocardial injury by ischemia/reperfusion (I/R) in vitro . Methods: Male Wistar rats (250-300g) were randomly divided into 3 groups submitted to I/R: control (CTR; n=5), exercised (EX; n=5) and exercised treated by naloxone, a non-selective opioid receptor antagonist (EX+NAL; n=5). The exercised groups underwent 4 consecutive days of treadmill training (60 min at 70% of maximal oxygen consumption). After the last exercise session (24h), the hearts were removed and immediately installed on a modified Langendorff apparatus. A latex balloon was inserted in the left ventricle (LV) to monitor the LV developed pressure (%LVDP). All hearts underwent a period of 30 min of sustained global ischemia followed by 1 h of reperfusion. After reperfusion, LV was sliced and incubated 20 min in triphenyltetrazolium to measure infarct size. Results: Anova two-way showed that CTR group presented a larger infarct area when compared to EXE group (32.9±9.2% vs 11.3±4.0% respectively; p<0.05). Naloxone treatment completely blocked the exercise-induced cardioprotection (28.1±8.0%). In respect to %LVDP, CTR and EXE+NAL showed significantly lower results compared to EXE group from 25 min of reperfusion. Conclusions: Our results indicate that opioid system is involved, at least in part, in cardioprotective effects of aerobic exercise in rats.

scholarly journals Cardioprotective Effect of Betulinic Acid on Myocardial Ischemia Reperfusion Injury in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Anzhou Xia ◽  
Zhi Xue ◽  
Yong Li ◽  
Wei Wang ◽  
Jieyun Xia ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Reperfusion Injury ◽  
Betulinic Acid ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tunel Assay ◽  
Sham Operation ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Objectives. This study aims to investigate the effect of betulinic acid (BA) on myocardial ischemia reperfusion/injury in an open-chest anesthetized rat model.Methods. The model was induced by 30 minutes left anterior descending occlusion followed by 2 hours reperfusion. There are six groups in our present study: sham operation group, ischemia/reperfusion group, low-dosage BA group, medium-dosage BA group, high-dosage BA group, and fosinopril sodium group. Rats in the latter four groups were administrated with BA (50, 100, and 200 mg/kg, i.g.) or fosinopril sodium (10 mg/kg, i.g.) once a day for 7 days before operation, respectively. Rats in the former two groups were given the same volume of vehicle (0.5% CMC-Na, i.g.). During the operation, cardiac function was continuously monitored. Serum LDH and CK were measured with colorimetric assays. The expression of Bcl-2 and Bax and the apoptosis of cardiomyocytes were investigated with western blot and TUNEL assay, respectively.Results. Pretreatment with BA improved cardiac function and attenuated LDH and CK activities compared with IR group. Further investigation demonstrated that the expression of Bcl-2 and Bax and TUNEL assay was in line with the above results.Conclusion. BA may reduce the release of LDH and CK, prevent cardiomyocytes apoptosis, and eventually alleviate the extent of the myocardial ischemia/reperfusion injury.

scholarly journals LncRNA CPhar Induces Cardiac Physiological Hypertrophy and Promotes Functional Recovery After Myocardial Ischemia-Reperfusion Injury

Circulation ◽  
2021 ◽  
Author(s):  
Rongrong Gao ◽  
Lijun Wang ◽  
Yihua Bei ◽  
Xiaodong Wu ◽  
Jiaqi Wang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Growth ◽  
Microarray Profiling ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Exercise Induced ◽  
Physiological Hypertrophy

Background: Exercise training's benefits in cardiovascular system have been well accepted, however, the underlying mechanism remains to be explored. Here, we report the initial functional characterization of an exercise-induced cardiac physiological hypertrophy associated novel lncRNA. Methods: Using lncRNA microarray profiling, we identified lncRNAs in contributing the modulation of exercise-induced cardiac growth that we termed Cardiac Physiological hypertrophy associated regulator (CPhar). Mice with Adeno-associated virus serotype 9 (AAV9) driving CPhar overexpression and knockdown were used in in-vivo experiments. Swim training was used to induce physiological cardiac hypertrophy in mice and ischemia reperfusion injury (IR/I) surgery was conducted to investigate the protective effects of CPhar in mice. To investigate the mechanisms of CPhar's function, we performed various analysis including RTqPCR, western blot, histology, cardiac function (by echocardiography), functional rescue experiments, mass spectrometry, in vitro RNA transcription, RNA pull down, RNA immunoprecipitation, chromatin immunoprecipitation assay, luciferase reporter assay, and coimmunoprecipitation assays. Results: We screened the lncRNAs in contributing the modulation of exercise-induced cardiac growth via lncRNA microarray profiling and found that CPhar was increased with exercise and was necessary for exercise-induced physiological cardiac growth. Gain- and loss- of function of CPhar regulated the expression of proliferation markers, hypertrophy, and apoptosis in cultured neonatal mouse cardiomyocytes (NMCMs). Overexpression of CPhar prevented myocardial ischemia reperfusion injury and cardiac dysfunction in vivo . We identified DDX17 as a binding partner of CPhar in regulating CPhar downstream factor ATF7 by sequestering C/EBPβ. Conclusions: Our study of this lncRNA CPhar provides new insights into the regulation of exercise-induced cardiac physiological growth, demonstrating the cardioprotective role of CPhar in the heart, as well as expanding our mechanistic understanding of lncRNA function.

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