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Article: Up-regulation of FoxO1 contributes to adverse vascular remodelling in type 1 diabetic rats

TitleUp-regulation of FoxO1 contributes to adverse vascular remodelling in type 1 diabetic rats
Authors
Keywordscardiovascular diseases
diabetes
Forkhead box protein O1
vascular remodeling
Issue Date2020
PublisherWiley Open Access for Foundation for Cellular and Molecular Medicine. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838
Citation
Journal of Cellular and Molecular Medicine, 2020, v. 24 n. 23, p. 13727-13738 How to Cite?
AbstractVascular complications from diabetes often result in poor outcomes for patients, even after optimized interventions. Forkhead box protein O1 (FoxO1) is a key regulator of cellular metabolism and plays an important role in vessel formation and maturation. Alterations of FoxO1 occur in the cardiovascular system in diabetes, yet the role of FoxO1 in diabetic vascular complications is poorly understood. In Streptozotocin (STZ)-induced type 1 diabetic rats, FoxO1 expression was up-regulated in carotid arteries at 8 weeks of diabetes that was accompanied with adverse vascular remodelling characterized as increased wall thickness, carotid medial cross-sectional area, media-to-lumen ratio and decreased carotid artery lumen area. This adverse vascular remodelling induced by hyperglycaemia in diabetic rats required FoxO1 activation as pharmacological inhibition of FoxO1 with 50mg/kg AS1842856 (AS) reversed vascular remodelling in type 1 diabetic rats. The adverse vascular remodelling in type 1 diabetes mellitus (T1DM) occurred concomitantly with increases in pro-inflammatory factors, adhesion factors, apoptosis, NOD-like receptor family protein-3 inflammasome activation and the phenotypic switch of arterial smooth muscle cells, which were all reversed by AS. In addition, FoxO1 inhibition counteracted the down-regulation of its upstream mediator PDK1 in T1DM. PDK1 activator reduced FoxO1 nuclear translocation, which serves as the basis for subsequent transcriptional regulation during hyperglycaemia. Taken together, our data suggest that FoxO1 is a critical trigger for type 1 diabetes-induced vascular remodelling in rats, and inhibition of FoxO1 thus offers a potential therapeutic option for diabetes-associated cardiovascular diseases.
Persistent Identifierhttp://hdl.handle.net/10722/293218
ISSN
2023 Impact Factor: 4.3
2023 SCImago Journal Rankings: 1.207
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLIU, J-
dc.contributor.authorXIE, X-
dc.contributor.authorYAN, D-
dc.contributor.authorWANG, Y-
dc.contributor.authorYuan, H-
dc.contributor.authorCai, Y-
dc.contributor.authorLuo, J-
dc.contributor.authorXu, A-
dc.contributor.authorHuang, Y-
dc.contributor.authorCheung, CW-
dc.contributor.authorIrwin, MG-
dc.contributor.authorXia, Z-
dc.date.accessioned2020-11-23T08:13:32Z-
dc.date.available2020-11-23T08:13:32Z-
dc.date.issued2020-
dc.identifier.citationJournal of Cellular and Molecular Medicine, 2020, v. 24 n. 23, p. 13727-13738-
dc.identifier.issn1582-1838-
dc.identifier.urihttp://hdl.handle.net/10722/293218-
dc.description.abstractVascular complications from diabetes often result in poor outcomes for patients, even after optimized interventions. Forkhead box protein O1 (FoxO1) is a key regulator of cellular metabolism and plays an important role in vessel formation and maturation. Alterations of FoxO1 occur in the cardiovascular system in diabetes, yet the role of FoxO1 in diabetic vascular complications is poorly understood. In Streptozotocin (STZ)-induced type 1 diabetic rats, FoxO1 expression was up-regulated in carotid arteries at 8 weeks of diabetes that was accompanied with adverse vascular remodelling characterized as increased wall thickness, carotid medial cross-sectional area, media-to-lumen ratio and decreased carotid artery lumen area. This adverse vascular remodelling induced by hyperglycaemia in diabetic rats required FoxO1 activation as pharmacological inhibition of FoxO1 with 50mg/kg AS1842856 (AS) reversed vascular remodelling in type 1 diabetic rats. The adverse vascular remodelling in type 1 diabetes mellitus (T1DM) occurred concomitantly with increases in pro-inflammatory factors, adhesion factors, apoptosis, NOD-like receptor family protein-3 inflammasome activation and the phenotypic switch of arterial smooth muscle cells, which were all reversed by AS. In addition, FoxO1 inhibition counteracted the down-regulation of its upstream mediator PDK1 in T1DM. PDK1 activator reduced FoxO1 nuclear translocation, which serves as the basis for subsequent transcriptional regulation during hyperglycaemia. Taken together, our data suggest that FoxO1 is a critical trigger for type 1 diabetes-induced vascular remodelling in rats, and inhibition of FoxO1 thus offers a potential therapeutic option for diabetes-associated cardiovascular diseases.-
dc.languageeng-
dc.publisherWiley Open Access for Foundation for Cellular and Molecular Medicine. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838-
dc.relation.ispartofJournal of Cellular and Molecular Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectcardiovascular diseases-
dc.subjectdiabetes-
dc.subjectForkhead box protein O1-
dc.subjectvascular remodeling-
dc.titleUp-regulation of FoxO1 contributes to adverse vascular remodelling in type 1 diabetic rats-
dc.typeArticle-
dc.identifier.emailCai, Y: caidavid@hku.hk-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.emailIrwin, MG: mgirwin@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityCheung, CW=rp00244-
dc.identifier.authorityIrwin, MG=rp00390-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1111/jcmm.15935-
dc.identifier.pmid33108705-
dc.identifier.pmcidPMC7754018-
dc.identifier.scopuseid_2-s2.0-85093974230-
dc.identifier.hkuros319063-
dc.identifier.volume24-
dc.identifier.issue23-
dc.identifier.spage13727-
dc.identifier.epage13738-
dc.identifier.isiWOS:000583937400001-
dc.publisher.placeUnited Kingdom-

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