Calpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathy

Calpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathy

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Summary: The relationship between diabetes and endothelial dysfunction Heart Bracelet Gift Box remains unclear, particularly the association with pathological activation of calpain, an intracellular cysteine protease.Here, we used human induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) to investigate the effects of diabetes on vascular health.Our results indicate that iPSC-ECs exposed to hyperglycemia had impaired autophagy, increased mitochondria fragmentation, and was associated with increased calpain activity.In addition, hyperglycemic iPSC-ECs had increased susceptibility to cell death when subjected to a secondary insult—simulated ischemia-reperfusion injury (sIRI).

Importantly, calpain inhibition restored autophagy and reduced mitochondrial fragmentation, concurrent with maintenance of ATP production, normalized reactive oxygen species levels and reduced susceptibility to sIRI.Using a human iPSC model of diabetic endotheliopathy, we demonstrated that restoration of autophagy and prevention of mitochondrial fragmentation via calpain inhibition improves vascular integrity.Our human iPSC-EC model thus represents a valuable platform to explore biological mechanisms and new treatments for diabetes-induced endothelial dysfunction.: In this article, Ong and colleagues used human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) as a novel disease modeling platform to study the effects of diabetes on vascular dysfunction and provided the cause for calpain inhibitors as an Halloween Spooky Basket anti-diabetic and cardioprotective drug.

Keywords: diabetes, endothelial dysfunction, iPSC, iPSC-ECs, calpain, autophagy, mitochondrial morphology, ischemia-reperfusion injury.