Frontiers in Cardiovascular Medicine (Mar 2024)

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

  • 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

DOI
https://doi.org/10.3389/fcvm.2024.1376367
Journal volume & issue
Vol. 11

Abstract

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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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