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<p>Mesenchymal stem-cell–derived exosomes (MSC-sEVs) represent a promising cell-free strategy for myocardial repair. Building upon the recent work by Bashir et al., we propose a complementary metabolic–lipid framework in which specific phospholipid cargoes allosterically regulate glucose-6-phosphate dehydrogenase (G6PD) to enhance pentose-phosphate-pathway (PPP) activity and sustain NADPH-dependent redox balance. Observations from LVAD-supported myocardium reveal coordinated up-regulation of G6PD-PPP enzymes during reverse remodeling, linking metabolic reprogramming to structural recovery. Lipid-mediated modulation of G6PD may therefore provide a pharmacologic bridge between exosome-based paracrine signaling and redox-driven myocardial regeneration, advancing metabolism-guided therapeutic design in heart failure.</p>

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Lipid-Mediated Exosomal Signaling Modulates G6PD-Dependent Metabolic Remodeling in Heart Failure

  • 期刊论文

  • 发表日期：

    2025年12月6日

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  • Xingyue Feng,
  • Dongjin Wang,
  • Can Xu

摘要

Mesenchymal stem-cell–derived exosomes (MSC-sEVs) represent a promising cell-free strategy for myocardial repair. Building upon the recent work by Bashir et al., we propose a complementary metabolic–lipid framework in which specific phospholipid cargoes allosterically regulate glucose-6-phosphate dehydrogenase (G6PD) to enhance pentose-phosphate-pathway (PPP) activity and sustain NADPH-dependent redox balance. Observations from LVAD-supported myocardium reveal coordinated up-regulation of G6PD-PPP enzymes during reverse remodeling, linking metabolic reprogramming to structural recovery. Lipid-mediated modulation of G6PD may therefore provide a pharmacologic bridge between exosome-based paracrine signaling and redox-driven myocardial regeneration, advancing metabolism-guided therapeutic design in heart failure.