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dc.contributor.authorOng, Sang-Bing
dc.contributor.authorLee, Won Hee
dc.contributor.authorShao, Ning-Yi
dc.contributor.authorIsmail, Nur Izzah
dc.contributor.authorKatwadi, Khairunnisa
dc.contributor.authorLim, Mim-Mim
dc.contributor.authorKwek, Xiu-Yi
dc.contributor.authorMichel, Nathaly Anto
dc.contributor.authorLi, Jiajun
dc.contributor.authorNewson, Jordan
dc.contributor.authorTahmasebi, Soroush
dc.contributor.authorRehman, Jalees
dc.contributor.authorKodo, Kazuki
dc.contributor.authorJang, Hye Ryoun
dc.contributor.authorOng, Sang-Ging
dc.date.accessioned2019-06-26T22:59:52Z
dc.date.available2019-06-26T22:59:52Z
dc.date.issued2019-03-05
dc.identifier.citationOng, S. B., Lee, W. H., Shao, N. Y., Ismail, N. I., Katwadi, K., Lim, M. M., ... & Tahmasebi, S. (2019). Calpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathy. Stem cell reports, 12(3), 597-610.en_US
dc.identifier.issn2213-6711
dc.identifier.pmid30799273
dc.identifier.doi10.1016/j.stemcr.2019.01.017
dc.identifier.urihttp://hdl.handle.net/10150/633036
dc.description.abstractThe 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.en_US
dc.description.sponsorshipSingapore Ministry of Health's National Medical Research Council Open Fund-Young Individual Research Grant [NMRC/OFYIRG/0021/2016]; Khoo Postdoctoral Fellowship Award [Duke-NUS-KPFA/2016/0010]; Hitachi Scholarship Research Support Grant from the Hitachi Global Foundation, Japan [RS-13, H-1]; American Heart Association Scientist Development Grant [16SDG27560003]; Stanford Diabetes Research Center under NIH [P30DK116074]; Frontier Research Grant 2017 from the Frontier Science Research Cluster (FSRC), Universiti Malaya, Malaysia [FG021-17AFR]; NIH [R01HL126516, R00HL130416]; Samsung Biomedical Research Institute [OTC 1180261]; National Research Foundation of Korea [NRF-2016R1A2B4008235]en_US
dc.language.isoenen_US
dc.publisherELSEVIER-CELL PRESSen_US
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S2213671119300190?via%3Dihuben_US
dc.rights© 2019 The Author(s).en_US
dc.subjectautophagyen_US
dc.subjectcalpainen_US
dc.subjectdiabetesen_US
dc.subjectendothelial dysfunctionen_US
dc.subjectiPSCen_US
dc.subjectiPSC-ECsen_US
dc.subjectischemia-reperfusion injuryen_US
dc.subjectmitochondrial morphologyen_US
dc.titleCalpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathyen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Basic Med Scien_US
dc.identifier.journalSTEM CELL REPORTSen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleStem cell reports
refterms.dateFOA2019-06-26T22:59:52Z


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