<p>Platelets are increasingly recognized as important mediators of cardioprotection during myocardial infarction and ischemia–reperfusion injury. This study investigated whether, under static hypoxia/reoxygenation (H/R) conditions, platelets and platelet-derived extracellular vesicles (PEVs) modulate matrix metalloproteinase (MMP) expression and activity in cardiomyocytes, contributing to myocardial protection effect. Cultured human cardiomyocytes (HCM) were subjected to static H/R either alone (control) or in co-culture with human platelets, and analysed across four hypoxia durations. Static H/R induced platelet activation and a time-dependent increase in CD61 expression on PEVs, accompanied by elevated proMMP-2 and MMP-2 activity in platelets. Co-cultured cardiomyocytes showed increased intracellular proMMP-2 and MMP-2 activity, while extracellular MMP-2 and MMP-9 activity was reduced. A trend toward decreased MMP-2 gene expression was also observed. Cardiomyocytes exposed to platelets demonstrated higher metabolic activity and extracellular lactate dehydrogenase levels, alongside reduced inducible nitric oxide synthase (iNOS) tissue expression compared with controls. Notably, CD61 expression on PEVs positively correlated with cardiomyocyte metabolic activity. These findings suggest that during H/R, platelet activation and PEVs release contribute to cardioprotective signaling pathways activation, potentially through adsorption of cardiomyocyte-derived MMPs, enhancement of cardiomyocyte metabolism, and inhibition of iNOS-associated cytotoxicity.</p>

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The influence of platelets and platelet-derived extracellular vesicles on the injury of cardiomyocytes under static hypoxia/reoxygenation conditions

  • Kornela Hałucha,
  • Marta Kamińska,
  • Paula Czyszczoń,
  • Agnieszka Sapa-Wojciechowska,
  • Alina Rak-Pasikowska,
  • Jolanta Łukasiewicz,
  • Iwona Bil-Lula

摘要

Platelets are increasingly recognized as important mediators of cardioprotection during myocardial infarction and ischemia–reperfusion injury. This study investigated whether, under static hypoxia/reoxygenation (H/R) conditions, platelets and platelet-derived extracellular vesicles (PEVs) modulate matrix metalloproteinase (MMP) expression and activity in cardiomyocytes, contributing to myocardial protection effect. Cultured human cardiomyocytes (HCM) were subjected to static H/R either alone (control) or in co-culture with human platelets, and analysed across four hypoxia durations. Static H/R induced platelet activation and a time-dependent increase in CD61 expression on PEVs, accompanied by elevated proMMP-2 and MMP-2 activity in platelets. Co-cultured cardiomyocytes showed increased intracellular proMMP-2 and MMP-2 activity, while extracellular MMP-2 and MMP-9 activity was reduced. A trend toward decreased MMP-2 gene expression was also observed. Cardiomyocytes exposed to platelets demonstrated higher metabolic activity and extracellular lactate dehydrogenase levels, alongside reduced inducible nitric oxide synthase (iNOS) tissue expression compared with controls. Notably, CD61 expression on PEVs positively correlated with cardiomyocyte metabolic activity. These findings suggest that during H/R, platelet activation and PEVs release contribute to cardioprotective signaling pathways activation, potentially through adsorption of cardiomyocyte-derived MMPs, enhancement of cardiomyocyte metabolism, and inhibition of iNOS-associated cytotoxicity.