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Area of Science:

  • Biochemistry
  • Cell Biology
  • Cardiology

Background:

  • Cardiovascular diseases and cancer are major global health burdens.
  • Doxorubicin (Doxo), a chemotherapy agent, induces cardiotoxicity, leading to long-term heart damage.
  • Small extracellular vesicles (sEVs) mediate intercellular communication and play a role in disease pathogenesis.

Purpose of the Study:

  • To investigate the role of sEVs from Doxo-treated breast cancer cells in inducing cardiomyocyte damage.
  • To explore the potential of these sEVs as biomarkers for early cardiotoxicity detection.

Main Methods:

  • Isolated sEVs from Doxo-treated and untreated MCF-7 breast cancer cells via ultracentrifugation.
  • Characterized sEVs using Nanoparticle Tracking Analysis (NTA), Scanning Electron Microscopy (SEM), and Western Blotting (WB).
  • Analyzed sEVs' cytokine cargo and assessed their impact on cardiomyocyte viability, function, and cellular stress markers (ROS, mitochondrial potential, calcium dynamics).

Main Results:

  • Doxo treatment significantly increased sEVs production from MCF-7 cells.
  • sEVs from Doxo-treated cells carried specific cytokine profiles.
  • Exposure to sEVs, particularly from Doxo-treated cells, reduced cardiomyocyte viability, impaired cell function, increased reactive oxygen species (ROS), and disrupted mitochondrial membrane potential and calcium homeostasis, indicating cardiotoxicity.

Conclusions:

  • Doxorubicin enhances the production of cardiotoxic sEVs from breast cancer cells.
  • These sEVs, through their cytokine cargo, contribute significantly to chemotherapy-induced cardiotoxicity.
  • Doxo-induced sEVs represent potential diagnostic biomarkers for early cardiotoxicity and therapeutic targets to mitigate cardiovascular risks.