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dc.contributor.authorAziz, A.
dc.contributor.authorHaywood, N.J.
dc.contributor.authorCordell, P.A.
dc.contributor.authorSmith, J.
dc.contributor.authorYuldasheva, N.Y.
dc.contributor.authorSengupta, A.
dc.contributor.authorAli, N.
dc.contributor.authorMercer, B.N.
dc.contributor.authorMughal, R.S.
dc.contributor.authorRiches-Suman, Kirsten
dc.contributor.authorCubbon, R.M.
dc.contributor.authorPorter, K.E.
dc.contributor.authorKearney, M.T.
dc.contributor.authorWheatcroft, S.B.
dc.date.accessioned2018-02-06T15:13:08Z
dc.date.available2018-02-06T15:13:08Z
dc.date.issued2018-02-01
dc.identifier.citationAziz A, Haywood NJ, Cordell PA et al (2018) Insulinlike growth factor – binding protein-1 improves vascular endothelial repair in male mice in the setting of insulin resistance. Endocrinology. 159(2): 696-709.en_US
dc.identifier.urihttp://hdl.handle.net/10454/14841
dc.descriptionYesen_US
dc.description.abstractInsulin resistance is associated with impaired endothelial regeneration in response to mechanical injury. We recently demonstrated that insulinlike growth factor–binding protein-1 (IGFBP1) ameliorated insulin resistance and increased nitric oxide generation in the endothelium. In this study, we hypothesized that IGFBP1 would improve endothelial regeneration and restore endothelial reparative functions in the setting of insulin resistance. In male mice heterozygous for deletion of insulin receptors, endothelial regeneration after femoral artery wire injury was enhanced by transgenic expression of human IGFBP1 (hIGFBP1). This was not explained by altered abundance of circulating myeloid angiogenic cells. Incubation of human endothelial cells with hIGFBP1 increased integrin expression and enhanced their ability to adhere to and repopulate denuded human saphenous vein ex vivo. In vitro, induction of insulin resistance by tumor necrosis factor α (TNFα) significantly inhibited endothelial cell migration and proliferation. Coincubation with hIGFBP1 restored endothelial migratory and proliferative capacity. At the molecular level, hIGFBP1 induced phosphorylation of focal adhesion kinase, activated RhoA and modulated TNFα-induced actin fiber anisotropy. Collectively, the effects of hIGFBP1 on endothelial cell responses and acceleration of endothelial regeneration in mice indicate that manipulating IGFBP1 could be exploited as a putative strategy to improve endothelial repair in the setting of insulin resistance.en_US
dc.description.sponsorshipFunded by a British Heart Foundation Clinical Research Training Fellowship for A.A. R.M.C. holds a British Heart Foundation Intermediate Clinical Research Fellowship. M.T.K. holds a British Heart Foundation Chair in Cardiology. S.B.W. holds a European Research Council Starting Grant.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1210/en.2017-00572en_US
dc.rights© 2018 Endocrine Society. This is a pre-copyedited, author-produced version of an article accepted for publication in Endocrinology following peer review. The version of record: Aziz A, Haywood NJ, Cordell PA et al (2018) Insulinlike growth factor – binding protein-1 improves vascular endothelial repair in male mice in the setting of insulin resistance. Endocrinology. 159(2): 696-709, is available online at: https://academic.oup.com/endo/article/159/2/696/4657266en_US
dc.subjectInsulin resistance; Animal modes of human disease; Growth factors/cytokines; Pathophysiology; Vascular biologyen_US
dc.titleInsulinlike growth factor – binding protein-1 improves vascular endothelial repair in male mice in the setting of insulin resistanceen_US
dc.status.refereedYesen_US
dc.date.Accepted2017-11-21
dc.date.application2017-11-24
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US


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