Regulation of phosphatase and tensin homolog on chromosome 10 in response to hypoxia

2012 ◽  
Vol 302 (9) ◽  
pp. H1806-H1817 ◽  
Author(s):  
Jinqiao Qian ◽  
Shukuan Ling ◽  
Alexander C. Castillo ◽  
Bo Long ◽  
Yochai Birnbaum ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Chromosome 10 ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Phosphatase and tensin homolog on chromosome 10 (PTEN) is downregulated during hypertrophic and cancerous cell growth, leading to activation of the prosurvival Akt pathway. However, PTEN regulation in cardiac myocytes upon exposure to hypoxia remains unclear. We explored the role of PTEN in response to hypoxia/ischemia in the myocardium. We validated that PTEN is a transcriptional target of activating transcription factor 2 (ATF-2) and is positively regulated via a p38/ATF-2 signaling pathway. Accordingly, hypoxia-induced upregulation of phosphorylation of ATF-2 and PTEN were reversed by a dominant negative mutant p38. Inhibition of PTEN in cardiomyocytes attenuated hypoxia-induced cell death and apoptosis. Cardiac-specific knockout of PTEN resulted in increased phosphorylation of Akt and forkhead box O 1 (forkhead transcription factors), limited infarct size in animals exposed to ischemia-reperfusion injury, and ameliorated deterioration of left ventricular function and remodeling following permanent coronary artery occlusion. In addition, the activation of Bim, FASL, and caspase was coupled with PTEN activation, all of which were attenuated by PTEN inhibition. In conclusion, cardiomyocyte-specific conditional PTEN deletion limited myocardial infarct size in an in vivo model of ischemia-reperfusion injury and attenuated adverse remodeling in a model of chronic permanent coronary artery ligation.

Long-term effect of low energy laser irradiation on infarction and reperfusion injury in the rat heart

2001 ◽  
Vol 90 (6) ◽  
pp. 2411-2419 ◽  
Author(s):  
Tali Yaakobi ◽  
Yariv Shoshany ◽  
Sara Levkovitz ◽  
Ofer Rubin ◽  
Shlomo A. Ben Haim ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Laser Irradiation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Low Energy ◽  
Energy Laser ◽  
Low Energy Laser

Low-energy laser irradiation (LELI) has been found to modulate biological processes. The present study investigated the effect of LELI on infarct size after chronic myocardial infarction (MI) and ischemia-reperfusion injury in rats. The left anterior descending (LAD) coronary artery was ligated in 83 rats to create MI or ischemia-reperfusion injury. The hearts of the laser-irradiated (LI) rats received irradiation after LAD coronary artery occlusion and 3 days post-MI. At 14, 21, and 45 days post-LAD coronary artery permanent occlusion, infarct sizes (percentage of left ventricular volume) in the non-laser-irradiated (NLI) rats were 52 ± 12 (SD), 47 ± 11, and 34 ± 7%, respectively, whereas in the LI rats they were significantly lower, being 20 ± 8, 15 ± 6, and 10 ± 4%, respectively. Left ventricular dilatation (LVD) in the chronic infarcted rats was significantly reduced (50–60%) in LI compared with NLI rats. LVD in the ischemia-reperfusion-injured LI rats was significantly reduced to a value that did not differ from intact normal noninfarcted rats. Laser irradiation caused a significant 2.2-fold elevation in the content of inducible heat shock proteins (specifically HSP70i) and 3.1-fold elevation in newly formed blood vessels in the heart compared with NLI rats. It is concluded that LELI caused a profound reduction in infarct size and LVD in the rat heart after chronic MI and caused complete reduction of LVD in ischemic-reperfused heart. This phenomenon may be partially explained by the cardioprotective effect of the HSP70i and enhanced angiogenesis in the myocardium after laser irradiation.

Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart

2013 ◽  
Vol 305 (4) ◽  
pp. H542-H550 ◽  
Author(s):  
Toshihiro Shinbo ◽  
Kenichi Kokubo ◽  
Yuri Sato ◽  
Shintaro Hagiri ◽  
Ryuji Hataishi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Left Ventricular ◽  
Hydrogen Gas ◽  
Coronary Artery Ligation

Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H2 is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H2 (2%), or NO + H2, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H2 alone. NO inhalation plus H2 reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H2 with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H2. In conclusion, breathing NO + H2 during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H2 gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.

Abstract 442: Intralipid Protects the Heart in Late Pregnancy Against Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis via Mir122 Induction

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jingyuan Li ◽  
Negar Motayagheni ◽  
Neusha Barakati ◽  
Mansoureh Eghbali
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Microarray Analysis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Late Pregnancy ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Microrna Microarray

The prevalence of coronary artery disease in late pregnancy (LP) has increased recently due to significant changes in women’s lifestyle patterns (age, stress, smoking, diabetes and chronic hypertension). Myocardial infarction during LP and the peripartum is associated with significant maternal mortality and morbidity compared to non pregnant women for unclear reasons. We have recently demonstrated that cardiac vulnerability to I/R injury drastically increases in LP rodents, leading to myocardial infarct size ~4 fold greater than in non-pregnant controls. We also discovered that administration of intralipid (an emulsion of soy bean oil, egg yolk phospholipids and glycerol) at reperfusion resulted in ~60% reduction in infarct size of the heart in LP rat subjected to I/R injury. However, the molecular mechanisms underlying intralipid-induced cardioprotection in late pregnancy is not clear. Here we hypothesized that intralipid protects the heart in late pregnancy by regulating the levels of specific microRNAs. The left anterior descending coronary artery was occluded in LP rats (21-22 days of pregnancy) for 45 min followed by 3 hr of reperfusion. One single bolus of PBS (control group) or 20% intralipid (intralipid group) was applied through the femoral vein 5 min before the reperfusion. The hearts of control and intralipid groups were used for microRNA microarray analysis (Ocean Ridge Biosciences). MicroRNA-microarray analysis identified MiR122 as a novel micro-RNA which its expression was strikingly upregulated more than 10 fold in the heart of LP rats in intralipid group compared to control group. miR122 regulates apoptosis in cardiomyocytes subjected to hypoxia/reoxygenation since miR122-overexpression resulted in reduced apoptosis, whereas knockdown of miR122 enhanced apoptosis. Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. Our data show that PKM2 and caspase 3 are two targets of miR122 since the expression of PKM2 and capase-3 in the heats subjected to I/R was significantly lower in intralipid group compared to control group in LP. In conclusion intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via inducing miR122 by targeting PKM2.

Blocking Na+/H+ exchange reduces [Na+]i and [Ca2+]i load after ischemia and improves function in intact hearts

2001 ◽  
Vol 281 (6) ◽  
pp. H2398-H2409 ◽  
Author(s):  
Jianzhong An ◽  
Srinivasan G. Varadarajan ◽  
Amadou Camara ◽  
Qun Chen ◽  
Enis Novalija ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ringer Solution ◽  
Left Ventricular ◽  
Isolated Hearts ◽  
Intracellular Ca ◽  
Ionic Basis

We determined in intact hearts whether inhibition of Na+/H+ exchange (NHE) decreases intracellular Na+ and Ca2+ during ischemia and reperfusion, improves function during reperfusion, and reduces infarct size. Guinea pig isolated hearts were perfused with Krebs-Ringer solution at 37°C. Left ventricular (LV) free wall intracellular Na+ concentration ([Na+]i) and intracellular Ca2+ concentration ([Ca2+]i) were measured using fluorescence dyes. Hearts were exposed to 30 min of ischemia with or without 10 μM of benzamide (BIIB-513), a selective NHE-1 inhibitor, infused for 10 min just before ischemia or for 10 min immediately on reperfusion. At 2 min of reperfusion, BIIB-513 given before ischemia decreased peak increases in [Na+]i and [Ca2+]i, respectively, from 2.5 and 2.3 times (controls) to 1.6 and 1.3 times preischemia values. At 30 min of reperfusion, BIIB-513 increased systolic-diastolic LV pressure (LVP) from 49 ± 2% (controls) to 80 ± 2% of preischemia values. BIIB-513 reduced ventricular fibrillation by 54% and reduced infarct size from 64 ± 1% to 20 ± 3%. First derivative of the LVP, O2 consumption, and cardiac efficiency were also improved by BIIB-513. Similar results were obtained with BIIB-513 given on reperfusion. These data show that Na+ loading is a marker of reperfusion injury in intact hearts in that inhibiting NHE reduces Na+ and Ca2+ loading during reperfusion while improving function. These results clearly implicate the ionic basis by which inhibiting NHE protects the guinea pig intact heart from ischemia-reperfusion injury.

PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated IκBα degradation

2001 ◽  
Vol 281 (6) ◽  
pp. H2612-H2618 ◽  
Author(s):  
Jialin Bao ◽  
Kaori Sato ◽  
Min Li ◽  
Youhe Gao ◽  
Ruhul Abid ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Adhesion Molecule ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Left Ventricular ◽  
Myeloperoxidase Activity ◽  
Intramyocardial Injection ◽  
Iκbα Degradation

PR-39 inhibits proteasome-mediated IκBα degradation and might protect against ischemia-reperfusion injury. We studied PR-39, its truncated form PR-11, and a mutant PR-11AAA, which lacks the ability to prevent IκBα degradation, in a rat heart ischemia-reperfusion model. After 30 min of ischemia and 24 h of reperfusion, cardiac function, infarct size, neutrophil infiltration, and myeloperoxidase activity were measured. Intramyocardial injection of 10 nmol/kg PR-39 or PR-11 at the time of reperfusion reduced infarct size by 65% and 57%, respectively, which improved blood pressure, left ventricular systolic pressure, and relaxation and contractility (±dP/d t) compared with vehicle controls 24 h later. Neutrophil infiltration, myeloperoxidase activity, and the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule 1 were reduced. Thus PR-39 and PR-11 effectively inhibit myocardial ischemia-reperfusion injury in the rat in vivo. This effect is mediated by inhibition of IκBα degradation and subsequent inhibition of nuclear factor-κB-dependent adhesion molecules. The active sequence is located in the first 11 amino acids, suggesting a potential for oligopeptide therapy as an adjunct to revascularization.

Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury

2004 ◽  
Vol 286 (5) ◽  
pp. H1923-H1935 ◽  
Author(s):  
James D. McCully ◽  
Hidetaka Wakiyama ◽  
Yng-Ju Hsieh ◽  
Mara Jones ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Parp Cleavage ◽  
Control Group ◽  
Early Reperfusion

Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia-reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff-perfused rabbit hearts ( n = 47) subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). The contribution of apoptosis was determined separately ( n = 42) using irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed pressure (LVPDP) and systolic shortening (SS) were significantly decreased and infarct size and TUNEL-positive cells were significantly increased ( P < 0.05 vs. Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3 and -9 activity significantly decreased ( P < 0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a significant increase in both necrosis and apoptosis ( P < 0.05 vs. Control group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic proapoptotic activation is evident early during ischemia but does not significantly contribute to infarct size before GI-25. The contribution of necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion, but this protection does not improve immediate postischemic functional recovery.

scholarly journals Apelin-13 limits infarct size and improves cardiac postischemic mechanical recovery only if given after ischemia

2011 ◽  
Vol 300 (6) ◽  
pp. H2308-H2315 ◽  
Author(s):  
Raffaella Rastaldo ◽  
Sandra Cappello ◽  
Anna Folino ◽  
Giovanni N. Berta ◽  
Andrea E. Sprio ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Protein Level ◽  
Ischemia Reperfusion Injury ◽  
Recovery Of Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Risk Area ◽  
Early Reperfusion ◽  
Mechanical Recovery

We studied whether apelin-13 is cardioprotective against ischemia/reperfusion injury if given as either a pre- or postconditioning mimetic and whether the improved postischemic mechanical recovery induced by apelin-13 depends only on the reduced infarct size or also on a recovery of function of the viable myocardium. We also studied whether nitric oxide (NO) is involved in apelin-induced protection and whether the reported ischemia-induced overexpression of the apelin receptor (APJ) plays a role in cardioprotection. Langendorff-perfused rat hearts underwent 30 min of global ischemia and 120 min of reperfusion. Left ventricular pressure was recorded. Infarct size and lactate dehydrogenase release were determined to evaluate the severity of myocardial injury. Apelin-13 was infused at 0.5 μM concentration for 20 min either before ischemia or in early reperfusion, without and with NO synthase inhibition by NG-nitro-l-arginine (l-NNA). In additional experiments, before ischemia also 1 μM apelin-13 was tested. APJ protein level was measured before and after ischemia. Whereas before ischemia apelin-13 (0.5 and 1.0 μM) was ineffective, after ischemia it reduced infarct size from 54 ± 2% to 26 ± 4% of risk area ( P < 0.001) and limited the postischemic myocardial contracture ( P < 0.001). l-NNA alone increased postischemic myocardial contracture. This increase was attenuated by apelin-13, which, however, was unable to reduce infarct size. Ischemia increased APJ protein level after 15-min perfusion, i.e., after most of reperfusion injury has occurred. Apelin-13 protects the heart only if given after ischemia. In this protection NO plays an important role. Apelin-13 efficiency as postconditioning mimetic cannot be explained by the increased APJ level.

Ebselen protects against ischemia-reperfusion injury in a canine model of myocardial infarction

1994 ◽  
Vol 267 (6) ◽  
pp. H2342-H2347 ◽  
Author(s):  
S. Hoshida ◽  
T. Kuzuya ◽  
M. Nishida ◽  
N. Yamashita ◽  
M. Hori ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Ischemic Myocardium ◽  
Regional Myocardial Blood Flow

We investigated the infarct-limiting effect of a selenoorganic compound, ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], in a canine coronary artery occlusion-reperfusion model of myocardial infarction. Ebselen, administered 1 h before coronary artery occlusion (50 mg/kg po), significantly reduced infarct size resulting from 90-min coronary artery occlusion followed by 5-h reperfusion (P < 0.05). When we examined the relation between infarct size and plasma ebselen level, infarct size in dogs with plasma ebselen level > 5 microM before reperfusion was significantly smaller (P < 0.05) than that in dogs with plasma ebselen level < or = 5 microM or in the control dogs. This infarct limitation produced by ebselen treatment was associated with an increase in reduced glutathione content and a reduction in myeloperoxidase activity in the ischemic myocardium. No differences between the control and treated groups were found in hemodynamic parameters or regional myocardial blood flow in the course of the experiment. The findings of this study demonstrate that ebselen effectively reduced the myocardial ischemia-reperfusion injury associated with preservation of the glutathione redox state and a reduction in neutrophil infiltration into the ischemic myocardium.

Isoflurane Produces Sustained Cardiac Protection after Ischemia–Reperfusion Injury in Mice

2006 ◽  
Vol 104 (3) ◽  
pp. 495-502 ◽  
Author(s):  
Yasuo M. Tsutsumi ◽  
Hemal H. Patel ◽  
N Chin Lai ◽  
Toshiyuki Takahashi ◽  
Brian P. Head ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Adenosine Triphosphate ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Cardiac Protection ◽  
Intact Mouse

Background Isoflurane reduces myocardial ischemia-reperfusion injury within hours to days of reperfusion. Whether isoflurane produces sustained cardiac protection has never been examined. The authors studied isoflurane-induced cardiac protection in the intact mouse after 2 h and 2 weeks of reperfusion and determined the dependence of this protection on adenosine triphosphate-dependent potassium channels and the relevance of this protection to myocardial function and apoptosis. Methods Mice were randomly assigned to receive oxygen or isoflurane for 30 min with 15 min of washout. Some mice received mitochondrial (5-hydroxydecanoic acid) or sarcolemmal (HMR-1098) adenosine triphosphate-dependent potassium channel blockers with or without isoflurane. Mice were then subjected to a 30-min coronary artery occlusion followed by 2 h or 2 weeks of reperfusion. Infarct size was determined at 2 h and 2 weeks of reperfusion. Cardiac function and apoptosis were determined 2 weeks after reperfusion. Results Isoflurane did not change hemodynamics. Isoflurane reduced infarct size after reperfusion when compared with the control groups (27.7 +/- 6.3 vs. 41.7 +/- 6.4% at 2 h and 19.6 +/- 5.9 vs. 28.8 +/- 9.0% at 2 weeks). Previous administration of 5-hydroxydecanoic acid, but not HMR-1098, abolished isoflurane-induced cardiac protection. At 2 weeks, left ventricular end-diastolic diameter was decreased significantly and end-systolic pressure and maximum and minimum dP/dt were improved by isoflurane. Isoflurane-treated mice subjected to ischemia and 2 weeks of reperfusion showed less expression of proapoptotic genes, significantly decreased expression of cleaved caspase-3, and significantly decreased deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive nuclei compared with the control group. Conclusions Cardiac protection induced by isoflurane against necrotic and apoptotic cell death is associated with an acute memory period that is sustained and functionally relevant 2 weeks after ischemia-reperfusion injury in mice in vivo.

Crocin-Elicited Autophagy Rescues Myocardial Ischemia/Reperfusion Injury via Paradoxical Mechanisms

2016 ◽  
Vol 44 (03) ◽  
pp. 515-530 ◽  
Author(s):  
Chao Zeng ◽  
Hu Li ◽  
Zhiwen Fan ◽  
Lei Zhong ◽  
Zhen Guo ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Apoptosis And Necrosis

Crocin, the main effective component of saffron, exerts protective effects against ischemia/reperfusion injury during strokes. However, the effects of crocin in myocardial ischemia/reperfusion injury, and the mechanisms involved, remain unknown. Pretreated with crocin for 7 days, C57BL/6N mice were subjected to 30 min of myocardial ischemia followed by 12[Formula: see text]h of reperfusion (for cardiac function and infarct size, cell apoptosis and necrosis). Neonatal mouse cardiomyocytes were subjected to 2 h of hypoxia followed by 4 h of reoxygenation. NMCM’s survival was assessed during hypoxia and reoxygenation in the presence or absence of the autophagy inhibitor 3-methyladenine or the inducer rapamycin. Western blotting was used to evaluate AMPK, Akt, and autophagy-related proteins. Autophagosome was observed using electron microscopy. In the in vivo experiment, crocin pretreatment significantly attenuated infarct size, myocardial apoptosis and necrosis, and improved left ventricular function following ischemia/reperfusion. In vitro data revealed that autophagy was induced during hypoxia, the levels of which were intensely elevated during reoxygenation. Crocin significantly promoted autophagy during ischemia, accompanied with the activation of AMPK. In contrast, crocin overtly inhibited autophagy during reperfusion, accompanied with Akt activation. Induction and inhibition of autophagy mitigated crocin induced protection against NMCMs injury during hypoxia and reoxygenation, respectively. Our data suggest that crocin demonstrated a myocardial protective effect via AMPK/mTOR and Akt/mTOR regulated autophagy against ischemia and reperfusion injury, respectively.

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