Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice

Recent animal study and clinical trial data suggested that remote limb ischemic postconditioning (RIPostC) can invoke potent cardioprotection. However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are po...

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Veröffentlicht in:PloS one 2014-01, Vol.9 (1), p.e86838-e86838
Hauptverfasser: Han, Zhihua, Cao, Jiatian, Song, Dongqiang, Tian, Lei, Chen, Kan, Wang, Yue, Gao, Lin, Yin, Zhaofang, Fan, Yuqi, Wang, Changqian
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creator Han, Zhihua
Cao, Jiatian
Song, Dongqiang
Tian, Lei
Chen, Kan
Wang, Yue
Gao, Lin
Yin, Zhaofang
Fan, Yuqi
Wang, Changqian
description Recent animal study and clinical trial data suggested that remote limb ischemic postconditioning (RIPostC) can invoke potent cardioprotection. However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. Streptozocin (STZ) induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND) and DM mice by three cycles of ischemia (5 min) and reperfusion (5 min) in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p
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However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. Streptozocin (STZ) induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND) and DM mice by three cycles of ischemia (5 min) and reperfusion (5 min) in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p&lt;0.05) and improved cardiac ejection fraction (49.70±3.46% in ND-RIPostC vs. 31.30±3.95% in ND-IR, p&lt;0.05). However, in DM group, no RIPostC mediated cardioprotetion effect was observed. To analyze the role of autophagy, western blot and immunohistochemistry was performed. Our data showed that a decreased sequestosome 1 (SQSTM1/p62) level, an increased Beclin-1 level, and higher ratio of LC3-II/LC3-I were observed in ND RIPostC group, but not DM RIPostC group. 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However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. Streptozocin (STZ) induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND) and DM mice by three cycles of ischemia (5 min) and reperfusion (5 min) in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p&lt;0.05) and improved cardiac ejection fraction (49.70±3.46% in ND-RIPostC vs. 31.30±3.95% in ND-IR, p&lt;0.05). However, in DM group, no RIPostC mediated cardioprotetion effect was observed. To analyze the role of autophagy, western blot and immunohistochemistry was performed. Our data showed that a decreased sequestosome 1 (SQSTM1/p62) level, an increased Beclin-1 level, and higher ratio of LC3-II/LC3-I were observed in ND RIPostC group, but not DM RIPostC group. 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control</subject><subject>Myocardium</subject><subject>Phagocytosis</subject><subject>Proteins</subject><subject>Reperfusion</subject><subject>Rodents</subject><subject>Streptozocin</subject><subject>Survival Rate</subject><subject>Veins &amp; arteries</subject><subject>Veterinary Science</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1padK0b1BaQ6G00N3oYEv2TWEJPSwEAj3dClke7WqxLUeSQ_eh-o6V9xDWJRfFFxKj7_9nNNYkyUuM5phyfLmxg-tkM-9tB3OEClbQ4lFyjktKZowg-vhkf5Y8836DUE4Lxp4mZyTLGCOMnid_FkOw_VqutqnxqenubHMHddykYQ2pkq42tnc2gArGdiloHXep1amDNkbTxrRVVKo1tEalvfVB2a42I2y6VRol7dbubGRz5OSlgx6cHvxoabrN4LZjxs66NlLRCD6k1RBiIKRRWEGI3mP4efJEy8bDi8N6kfz8_OnH1dfZ9c2X5dXieqZYScJMYlUqkKgExgBjXaBC86LOFMpzlHPGCSOV5hVkmjCdQ11SqipCMVc5juf0Inm99-0b68Wh017grMSUUI5GYrknais3onemlW4rrDRiF7BuJaSLZTcgqCyRwpLkuawyxKsCeFZVNaOc8KKqIXp9PGQbqhZqBV1wspmYTk86sxYreydoiRDLi2jw7mDg7O0APog2thqaRnZgh13dhCOel2Pdb_5BH77dgVrJeAHTaRvzqtFULDJeFDlGlEZq_gAVv3p8DPFZahPjE8H7iSAyAX6HlRy8F8vv3_6fvfk1Zd-esGuQTVh72wzjK_RTMNuDylnvHej7JmMkxqk6dkOMUyUOUxVlr05_0L3oOEb0L8b4IKU</recordid><startdate>20140123</startdate><enddate>20140123</enddate><creator>Han, Zhihua</creator><creator>Cao, Jiatian</creator><creator>Song, Dongqiang</creator><creator>Tian, Lei</creator><creator>Chen, Kan</creator><creator>Wang, Yue</creator><creator>Gao, Lin</creator><creator>Yin, Zhaofang</creator><creator>Fan, Yuqi</creator><creator>Wang, Changqian</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140123</creationdate><title>Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice</title><author>Han, Zhihua ; 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However, during ischemia reperfusion injury (IR), the effect and mechanism of RIPostC on myocardium in subjects with or without diabetes mellitus (DM) are poorly understood. Autophagy plays a crucial role in alleviating myocardial IR injury. The aim of this study was to determine the effect of RIPostC on mice myocardial IR injury model with or without DM, and investigate the role of autophagy in this process. Streptozocin (STZ) induced DM mice model and myocardial IR model were established. Using a noninvasive technique, RIPostC was induced in normal mice (ND) and DM mice by three cycles of ischemia (5 min) and reperfusion (5 min) in the left hindlimb. In ND group, RIPostC significantly reduced infarct size (32.6±3.0% in ND-RIPostC vs. 50.6±2.4% in ND-IR, p&lt;0.05) and improved cardiac ejection fraction (49.70±3.46% in ND-RIPostC vs. 31.30±3.95% in ND-IR, p&lt;0.05). However, in DM group, no RIPostC mediated cardioprotetion effect was observed. To analyze the role of autophagy, western blot and immunohistochemistry was performed. Our data showed that a decreased sequestosome 1 (SQSTM1/p62) level, an increased Beclin-1 level, and higher ratio of LC3-II/LC3-I were observed in ND RIPostC group, but not DM RIPostC group. The current study suggested that RIPostC exerts cardioprotection effect on IR in normal mice, but not DM mice, and this difference is via, at least in part, the up-regulation of autophagy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24466263</pmid><doi>10.1371/journal.pone.0086838</doi><tpages>e86838</tpages><oa>free_for_read</oa></addata></record>
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subjects Analysis
Animals
Autophagy
Biology
Blotting, Western
Cardiology
Cardiotonic Agents
Cell death
Clinical trials
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - mortality
Diabetes Mellitus, Experimental - pathology
Disease Models, Animal
Echocardiography
Glucose
Heart attacks
Heart diseases
Hindlimb - blood supply
Hospitals
Immunoenzyme Techniques
Immunohistochemistry
Injuries
Ischemia
Ischemic Preconditioning, Myocardial
Kinases
Laboratory animals
Male
Medical research
Medical schools
Medicine
Mice
Mice, Inbred C57BL
Mortality
Myocardial ischemia
Myocardial Reperfusion Injury - mortality
Myocardial Reperfusion Injury - pathology
Myocardial Reperfusion Injury - prevention & control
Myocardium
Phagocytosis
Proteins
Reperfusion
Rodents
Streptozocin
Survival Rate
Veins & arteries
Veterinary Science
title Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/reperfusion injury in normal mice, but not diabetic mice
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