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dc.contributor.authorEl-Osta, A
dc.contributor.authorBrasacchio, D
dc.contributor.authorYao, D
dc.contributor.authorPocai, A
dc.contributor.authorJones, PL
dc.contributor.authorRoeder, RG
dc.contributor.authorCooper, ME
dc.contributor.authorBrownlee, M
dc.date.accessioned2020-12-18T03:04:10Z
dc.date.available2020-12-18T03:04:10Z
dc.date.issued2008-09-29
dc.identifierpii: jem.20081188
dc.identifier.citationEl-Osta, A., Brasacchio, D., Yao, D., Pocai, A., Jones, P. L., Roeder, R. G., Cooper, M. E. & Brownlee, M. (2008). Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. JOURNAL OF EXPERIMENTAL MEDICINE, 205 (10), pp.2409-2417. https://doi.org/10.1084/jem.20081188.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/255616
dc.description.abstractThe current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor kappaB (NF-kappaB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-kappaB-induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced alpha-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.titleTransient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia
dc.typeJournal Article
dc.identifier.doi10.1084/jem.20081188
melbourne.affiliation.departmentClinical Pathology
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume205
melbourne.source.issue10
melbourne.source.pages2409-2417
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1293001
melbourne.contributor.authorEl-Osta, Assam
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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