Myocardial hypothermia increases autophagic flux, mitochondrial mass and myocardial function after ischemia-reperfusion injury
Identifieur interne : 000611 ( Main/Exploration ); précédent : 000610; suivant : 000612Myocardial hypothermia increases autophagic flux, mitochondrial mass and myocardial function after ischemia-reperfusion injury
Auteurs : Stefanie Marek-Iannucci [États-Unis] ; Amandine Thomas [États-Unis] ; Jean Hou [États-Unis] ; Annunziata Crupi [États-Unis] ; Jon Sin [États-Unis] ; David J. Taylor [États-Unis] ; Lawrence S. Czer [États-Unis] ; Fardad Esmailian [États-Unis] ; Robert M. Mentzer [États-Unis] ; Allen M. Andres [États-Unis] ; Roberta A. Gottlieb [États-Unis]Source :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
Animal studies have demonstrated beneficial effects of therapeutic hypothermia on myocardial function, yet exact mechanisms remain unclear. Impaired autophagy leads to heart failure and mitophagy is important for mitigating ischemia/reperfusion injury. This study aims to investigate whether the beneficial effects of therapeutic hypothermia are due to preserved autophagy and mitophagy. Under general anesthesia, the left anterior descending coronary artery of 19 female farm pigs was occluded for 90 minutes with consecutive reperfusion. 30 minutes after reperfusion, we performed pericardial irrigation with warm or cold saline for 60 minutes. Myocardial tissue analysis was performed one and four weeks after infarction. Therapeutic hypothermia induced a significant increase in autophagic flux, mitophagy, mitochondrial mass and function in the myocardium after infarction. Cell stress, apoptosis, inflammation as well as fibrosis were reduced, with significant preservation of systolic and diastolic function four weeks post infarction. We found similar biochemical changes in human samples undergoing open chest surgery under hypothermic conditions when compared to the warm. These results suggest that autophagic flux and mitophagy are important mechanisms implicated in cardiomyocyte recovery after myocardial infarction under hypothermic conditions. New therapeutic strategies targeting these pathways directly could lead to improvements in prevention of heart failure.
Url:
DOI: 10.1038/s41598-019-46452-w
PubMed: 31292486
PubMed Central: 6620356
Affiliations:
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Czer</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2152 9905</institution-id><institution-id institution-id-type="GRID">grid.50956.3f</institution-id><institution>Smidt Heart Institute, Cedars-Sinai Medical Center,</institution></institution-wrap>Los Angeles, California USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Esmailian, Fardad" sort="Esmailian, Fardad" uniqKey="Esmailian F" first="Fardad" last="Esmailian">Fardad Esmailian</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2152 9905</institution-id><institution-id institution-id-type="GRID">grid.50956.3f</institution-id><institution>Smidt Heart Institute, Cedars-Sinai Medical Center,</institution></institution-wrap>Los Angeles, California USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Los Angeles</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2152 9905</institution-id><institution-id institution-id-type="GRID">grid.50956.3f</institution-id><institution>Division of Cardiac Surgery, Cedars-Sinai Medical Center,</institution></institution-wrap>Los Angeles, California USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Mentzer, Robert M" sort="Mentzer, Robert M" uniqKey="Mentzer R" first="Robert M." last="Mentzer">Robert M. Mentzer</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2152 9905</institution-id><institution-id institution-id-type="GRID">grid.50956.3f</institution-id><institution>Smidt Heart Institute, Cedars-Sinai Medical Center,</institution></institution-wrap>Los Angeles, California USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Andres, Allen M" sort="Andres, Allen M" uniqKey="Andres A" first="Allen M." last="Andres">Allen M. Andres</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2152 9905</institution-id><institution-id institution-id-type="GRID">grid.50956.3f</institution-id><institution>Smidt Heart Institute, Cedars-Sinai Medical Center,</institution></institution-wrap>Los Angeles, California USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Gottlieb, Roberta A" sort="Gottlieb, Roberta A" uniqKey="Gottlieb R" first="Roberta A." last="Gottlieb">Roberta A. Gottlieb</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2152 9905</institution-id><institution-id institution-id-type="GRID">grid.50956.3f</institution-id><institution>Smidt Heart Institute, Cedars-Sinai Medical Center,</institution></institution-wrap>Los Angeles, California USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Los Angeles</wicri:cityArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Animal studies have demonstrated beneficial effects of therapeutic hypothermia on myocardial function, yet exact mechanisms remain unclear. Impaired autophagy leads to heart failure and mitophagy is important for mitigating ischemia/reperfusion injury. This study aims to investigate whether the beneficial effects of therapeutic hypothermia are due to preserved autophagy and mitophagy. Under general anesthesia, the left anterior descending coronary artery of 19 female farm pigs was occluded for 90 minutes with consecutive reperfusion. 30 minutes after reperfusion, we performed pericardial irrigation with warm or cold saline for 60 minutes. Myocardial tissue analysis was performed one and four weeks after infarction. Therapeutic hypothermia induced a significant increase in autophagic flux, mitophagy, mitochondrial mass and function in the myocardium after infarction. Cell stress, apoptosis, inflammation as well as fibrosis were reduced, with significant preservation of systolic and diastolic function four weeks post infarction. We found similar biochemical changes in human samples undergoing open chest surgery under hypothermic conditions when compared to the warm. These results suggest that autophagic flux and mitophagy are important mechanisms implicated in cardiomyocyte recovery after myocardial infarction under hypothermic conditions. New therapeutic strategies targeting these pathways directly could lead to improvements in prevention of heart failure.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Dai, W" uniqKey="Dai W">W Dai</name></author><author><name sortKey="Herring, Mj" uniqKey="Herring M">MJ Herring</name></author><author><name sortKey="Hale, Sl" uniqKey="Hale S">SL Hale</name></author><author><name sortKey="Kloner, Ra" uniqKey="Kloner R">RA Kloner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, J" uniqKey="Shi J">J Shi</name></author><author><name sortKey="Dai, W" uniqKey="Dai W">W Dai</name></author><author><name sortKey="Kloner, Ra" uniqKey="Kloner R">RA Kloner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dash, R" uniqKey="Dash R">R Dash</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hale, Sl" uniqKey="Hale 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uniqKey="Middleton K">KJ Middleton</name></author><author><name sortKey="Kopelen, Ha" uniqKey="Kopelen H">HA Kopelen</name></author><author><name sortKey="Zoghbi, Wa" uniqKey="Zoghbi W">WA Zoghbi</name></author><author><name sortKey="Qui Ones, Ma" uniqKey="Qui Ones M">MA Quiñones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andres, Am" uniqKey="Andres A">AM Andres</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hadi, Am" uniqKey="Hadi A">AM Hadi</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Campos, Jc" uniqKey="Campos J">JC Campos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rogers, Gw" uniqKey="Rogers G">GW Rogers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boren, J" uniqKey="Boren J">J Boren</name></author><author><name sortKey="Brindle, Km" uniqKey="Brindle K">KM Brindle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, Je" uniqKey="Adams J">JE Adams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klionsky, Dj" uniqKey="Klionsky D">DJ Klionsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Minowa Nozawa, A" uniqKey="Minowa Nozawa A">A Minowa-Nozawa</name></author><author><name sortKey="Nozawa, T" uniqKey="Nozawa T">T Nozawa</name></author><author><name sortKey="Okamoto Furuta, K" uniqKey="Okamoto Furuta K">K Okamoto-Furuta</name></author><author><name sortKey="Kohda, H" uniqKey="Kohda H">H Kohda</name></author><author><name sortKey="Nakagawa, I" uniqKey="Nakagawa I">I Nakagawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Callegari, S" uniqKey="Callegari S">S Callegari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pfleger, J" uniqKey="Pfleger J">J Pfleger</name></author><author><name sortKey="He, M" uniqKey="He M">M He</name></author><author><name sortKey="Abdellatif, M" uniqKey="Abdellatif M">M Abdellatif</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheeran, Fl" uniqKey="Sheeran F">FL Sheeran</name></author><author><name sortKey="Pepe, S" uniqKey="Pepe S">S Pepe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arnaud, C" uniqKey="Arnaud C">C Arnaud</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Marek Iannucci, Stefanie" sort="Marek Iannucci, Stefanie" uniqKey="Marek Iannucci S" first="Stefanie" last="Marek-Iannucci">Stefanie Marek-Iannucci</name></region><name sortKey="Andres, Allen M" sort="Andres, Allen M" uniqKey="Andres A" first="Allen M." last="Andres">Allen M. Andres</name><name sortKey="Crupi, Annunziata" sort="Crupi, Annunziata" uniqKey="Crupi A" first="Annunziata" last="Crupi">Annunziata Crupi</name><name sortKey="Czer, Lawrence S" sort="Czer, Lawrence S" uniqKey="Czer L" first="Lawrence S." last="Czer">Lawrence S. Czer</name><name sortKey="Esmailian, Fardad" sort="Esmailian, Fardad" uniqKey="Esmailian F" first="Fardad" last="Esmailian">Fardad Esmailian</name><name sortKey="Esmailian, Fardad" sort="Esmailian, Fardad" uniqKey="Esmailian F" first="Fardad" last="Esmailian">Fardad Esmailian</name><name sortKey="Gottlieb, Roberta A" sort="Gottlieb, Roberta A" uniqKey="Gottlieb R" first="Roberta A." last="Gottlieb">Roberta A. Gottlieb</name><name sortKey="Hou, Jean" sort="Hou, Jean" uniqKey="Hou J" first="Jean" last="Hou">Jean Hou</name><name sortKey="Mentzer, Robert M" sort="Mentzer, Robert M" uniqKey="Mentzer R" first="Robert M." last="Mentzer">Robert M. Mentzer</name><name sortKey="Sin, Jon" sort="Sin, Jon" uniqKey="Sin J" first="Jon" last="Sin">Jon Sin</name><name sortKey="Taylor, David J" sort="Taylor, David J" uniqKey="Taylor D" first="David J." last="Taylor">David J. Taylor</name><name sortKey="Thomas, Amandine" sort="Thomas, Amandine" uniqKey="Thomas A" first="Amandine" last="Thomas">Amandine Thomas</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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