ArticleStem cell reports2019
Calpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathy.
Article in Stem cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Exploring Autophagy Inducing Molecules: Targeting Diverse Pathways in Alzheimer's Disease Management.Medicinal research reviews · 2026Review
- TRPC6-Calpain-1 Axis Promotes Tubulointerstitial Inflammation by Inhibiting Mitophagy in Diabetic Kidney Disease.Kidney international reports · 2024Article
- Tissue-Engineered Microvessels: A Review of Current Engineering Strategies and Applications.Advanced healthcare materials · 2024Review
- iPSC-Derived Endothelial Cells Reveal LDLR Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia.International journal of molecular sciences · 2024Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.Cardiovascular research · 2023Article
- Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy.Cardiovascular research · 2023Review
- Rescue of EndMT-associated endothelial dysfunction by modulating the YAP pathway.Nature cardiovascular research · 2023Article
- Statins improve endothelial function via suppression of epigenetic-driven EndMT.Nature cardiovascular research · 2023Article
- Endothelial Autophagy Dysregulation in Diabetes.Cells · 2023Review
- Alteration of the NEpigenomics · 2022Article
- Review
- Inhibition of calpain reduces cell apoptosis by suppressing mitochondrial fission in acute viral myocarditis.Cell biology and toxicology · 2022Article
- Involvement of Cdkal1 in the etiology of type 2 diabetes mellitus and microvascular diabetic complications: a review.Journal of diabetes and metabolic disorders · 2022Review
- Impaired autophagy with augmented apoptosis in a Th1/Th2-imbalanced placental micromilieu is associated with spontaneous preterm birth.Frontiers in molecular biosciences · 2022Article
- Article
- Patient-specific iPSC-derived endothelial cells reveal aberrant p38 MAPK signaling in atypical hemolytic uremic syndrome.Stem cell reports · 2021Article
- Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease.Cells · 2021Review
- Adipocyte-Derived Extracellular Vesicles: State of the Art.International journal of molecular sciences · 2021Review
- Development and Application of Endothelial Cells Derived From Pluripotent Stem Cells in Microphysiological Systems Models.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 5 countries.
Funding
Abstract
The relationship between diabetes and endothelial dysfunction 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.