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dc.contributor.authorBlanco, F
dc.contributor.authorHeinonen, SE
dc.contributor.authorGurzeler, E
dc.contributor.authorBerglund, LM
dc.contributor.authorDutius Andersson, AM
dc.contributor.authorKotova, O
dc.contributor.authorJönsson-Rylander, AC
dc.contributor.authorYlä-Herttuala, S
dc.contributor.authorGomez, MF
dc.date.accessioned2018-04-09T12:39:25Z
dc.date.available2018-04-09T12:39:25Z
dc.date.issued2018
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/6246
dc.description.abstractAims: Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated the effects of nuclear factor of activated T-cells inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease. Methods & Results: IGF-II/LDLR–/–ApoB100/100 mice were generated by crossbreeding low-density lipoprotein receptor–deficient mice that synthesize only apolipoprotein B100 (LDLR–/–ApoB100/100) with transgenic mice overexpressing insulin-like growth factor-II in pancreatic β cells. Mice have mild hyperglycaemia and hyperinsulinaemia and develop complex atherosclerotic lesions. In vivo treatment with the nuclear factor of activated T-cells blocker A-285222 for 4 weeks reduced atherosclerotic plaque area and degree of stenosis in the brachiocephalic artery of IGF-II/LDLR–/–ApoB100/100 mice, as assessed non-invasively using ultrasound biomicroscopy prior and after treatment, and histologically after termination. Treatment had no impact on plaque composition (i.e. muscle, collagen, macrophages). The reduced plaque area could not be explained by effects of A-285222 on plasma glucose, insulin or lipids. Inhibition of nuclear factor of activated T-cells was associated with increased expression of atheroprotective NOX4 and of the anti-oxidant enzyme catalase in aortic vascular smooth muscle cells. Conclusion: Targeting the nuclear factor of activated T-cells signalling pathway may be an attractive approach for the treatment of diabetic macrovascular complications.
dc.language.isoEN
dc.publisherSAGE Publications
dc.relation.ispartofseriesDIABETES AND VASCULAR DISEASE RESEARCH
dc.relation.urihttp://dx.doi.org/10.1177/1479164118759220
dc.rightsCC BY-NC http://creativecommons.org/licenses/by-nc/4.0/
dc.subjectatherosclerosis
dc.subjectoxidative stress
dc.subjecttype 2 diabetes
dc.subjectnuclear factor of activated T-cells
dc.subjecthyperglycaemia
dc.subjectApoB100
dc.titleIn vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR-/-ApoB100/100 mice
dc.description.versionpublished version
dc.contributor.departmentA.I. Virtanen -instituutti
uef.solecris.id53010291en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Authors
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-JTI/115006/EU/SUrrogate markers for vascular Micro- and Macrovascular hard endpoints for Innovative diabetes Tools/SUMMIT
dc.relation.doi10.1177/1479164118759220
dc.description.reviewstatuspeerReviewed
dc.relation.issn1479-1641
dc.relation.volumeFirst Published March 2. 2018
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessHybridijulkaisukanavassa ilmestynyt avoin julkaisu


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