Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats

Background and aimsIschemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without per...

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Main Authors: Ahmed Elmahdy, Aaron Shekka Espinosa, Yalda Kakaei, Tetiana Pylova, Abhishek Jha, Ermir Zulfaj, Maryna Krasnikova, Amin Al-Awar, Zahra Sheybani, Valentyna Sevastianova, Evelin Berger, Amirali Nejat, Linnea Molander, Erik Axel Andersson, Elmir Omerovic, Shafaat Hussain, Björn Redfors
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2024.1376367/full
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author Ahmed Elmahdy
Ahmed Elmahdy
Aaron Shekka Espinosa
Aaron Shekka Espinosa
Yalda Kakaei
Yalda Kakaei
Tetiana Pylova
Tetiana Pylova
Abhishek Jha
Abhishek Jha
Ermir Zulfaj
Maryna Krasnikova
Maryna Krasnikova
Amin Al-Awar
Amin Al-Awar
Zahra Sheybani
Zahra Sheybani
Valentyna Sevastianova
Valentyna Sevastianova
Evelin Berger
Amirali Nejat
Linnea Molander
Linnea Molander
Erik Axel Andersson
Erik Axel Andersson
Elmir Omerovic
Elmir Omerovic
Shafaat Hussain
Shafaat Hussain
Björn Redfors
Björn Redfors
Björn Redfors
author_facet Ahmed Elmahdy
Ahmed Elmahdy
Aaron Shekka Espinosa
Aaron Shekka Espinosa
Yalda Kakaei
Yalda Kakaei
Tetiana Pylova
Tetiana Pylova
Abhishek Jha
Abhishek Jha
Ermir Zulfaj
Maryna Krasnikova
Maryna Krasnikova
Amin Al-Awar
Amin Al-Awar
Zahra Sheybani
Zahra Sheybani
Valentyna Sevastianova
Valentyna Sevastianova
Evelin Berger
Amirali Nejat
Linnea Molander
Linnea Molander
Erik Axel Andersson
Erik Axel Andersson
Elmir Omerovic
Elmir Omerovic
Shafaat Hussain
Shafaat Hussain
Björn Redfors
Björn Redfors
Björn Redfors
author_sort Ahmed Elmahdy
collection DOAJ
description Background and aimsIschemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function.Methods and resultsRats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding.ConclusionIPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.
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spelling doaj.art-015b6376ee204eecbd09715653d0c6092024-03-15T04:50:05ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2024-03-011110.3389/fcvm.2024.13763671376367Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in ratsAhmed Elmahdy0Ahmed Elmahdy1Aaron Shekka Espinosa2Aaron Shekka Espinosa3Yalda Kakaei4Yalda Kakaei5Tetiana Pylova6Tetiana Pylova7Abhishek Jha8Abhishek Jha9Ermir Zulfaj10Maryna Krasnikova11Maryna Krasnikova12Amin Al-Awar13Amin Al-Awar14Zahra Sheybani15Zahra Sheybani16Valentyna Sevastianova17Valentyna Sevastianova18Evelin Berger19Amirali Nejat20Linnea Molander21Linnea Molander22Erik Axel Andersson23Erik Axel Andersson24Elmir Omerovic25Elmir Omerovic26Shafaat Hussain27Shafaat Hussain28Björn Redfors29Björn Redfors30Björn Redfors31Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenProteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Cardiology, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenWallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenDepartment of Cardiology, Sahlgrenska University Hospital, Gothenburg, SwedenBackground and aimsIschemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function.Methods and resultsRats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding.ConclusionIPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.https://www.frontiersin.org/articles/10.3389/fcvm.2024.1376367/fullmyocardial infarctionmyocardial stunningischemic preconditioningechocardiographyspeckle tracking analysisphosphoproteomics
spellingShingle Ahmed Elmahdy
Ahmed Elmahdy
Aaron Shekka Espinosa
Aaron Shekka Espinosa
Yalda Kakaei
Yalda Kakaei
Tetiana Pylova
Tetiana Pylova
Abhishek Jha
Abhishek Jha
Ermir Zulfaj
Maryna Krasnikova
Maryna Krasnikova
Amin Al-Awar
Amin Al-Awar
Zahra Sheybani
Zahra Sheybani
Valentyna Sevastianova
Valentyna Sevastianova
Evelin Berger
Amirali Nejat
Linnea Molander
Linnea Molander
Erik Axel Andersson
Erik Axel Andersson
Elmir Omerovic
Elmir Omerovic
Shafaat Hussain
Shafaat Hussain
Björn Redfors
Björn Redfors
Björn Redfors
Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
Frontiers in Cardiovascular Medicine
myocardial infarction
myocardial stunning
ischemic preconditioning
echocardiography
speckle tracking analysis
phosphoproteomics
title Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
title_full Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
title_fullStr Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
title_full_unstemmed Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
title_short Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
title_sort ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats
topic myocardial infarction
myocardial stunning
ischemic preconditioning
echocardiography
speckle tracking analysis
phosphoproteomics
url https://www.frontiersin.org/articles/10.3389/fcvm.2024.1376367/full
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