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dc.contributor.authorWadey, Rebecca
dc.contributor.authorConnolly, Katherine
dc.contributor.authorMathew, Donna
dc.contributor.authorWalters, Gareth
dc.contributor.authorRees, Aled
dc.contributor.authorJames, Philip
dc.date.accessioned2019-04-09T07:56:09Z
dc.date.available2019-04-09T07:56:09Z
dc.date.issued2019-01-24
dc.identifier.citationWadey, R.M., Connolly, K.D., Mathew, D., Walters, G., Rees, D.A. and James, P.E. (2019) 'Inflammatory adipocyte-derived extracellular vesicles promote leukocyte attachment to vascular endothelial cells', Atherosclerosis, 283, p.19-27. DOI: 10.1016/j.atherosclerosis.2019.01.013.en_US
dc.identifier.issn1879-1484
dc.identifier.urihttp://hdl.handle.net/10369/10411
dc.descriptionArticle published in Atherosclerosis on 24 January 2019 (online), available at: https://doi.org/10.1016/j.atherosclerosis.2019.01.013.en_US
dc.description.abstractBackground and aims. Obesity is associated with an increased risk of cardiovascular disease, but the mechanisms involved are not completely understood. In obesity, the adipocyte microenvironment is characterised by both hypoxia and inflammation. Therefore, we sought to determine whether extracellular vesicles (EVs) derived from adipocytes in this setting might be involved in mediating cardiovascular disease, specifically by promoting leukocyte attachment to vascular endothelial cells. Methods. Mature 3T3-L1 adipocytes were incubated for 24 h under control, TNF-α (30 ng/mL), hypoxia (1% O2), or TNF-α+hypoxia (30 ng/mL, 1% O2) conditions. EVs were isolated by differential ultracentrifugation and analysed by nanoparticle tracking analysis. Primary human umbilical vein endothelial cells (HUVECs) were treated with EVs for 6 h before being lysed for Western blotting to investigate changes in adhesion molecule production, or for use in leukocyte attachment assays. Results. EVs from adipocytes treated with TNF-α and TNF-α+hypoxia increased vascular cell adhesion molecule (VCAM-1) production in HUVECs compared to basal level (4.2 ± 0.6 and 3.8 ± 0.3-fold increase, respectively (p < 0.05)), an effect that was inhibited by an anti-TNF-α neutralising antibody. Production of other adhesion molecules (E-selectin, P-selectin, platelet endothelial cell adhesion molecule and VE-Cadherin) was unchanged. Pre-incubating HUVECs with TNF-α+hypoxia EVs significantly increased leukocyte attachment compared to basal level (3.0 ± 0.4-fold increase (p < 0.05)). Conclusions. Inflammatory adipocyte EVs induce VCAM-1 production in vascular endothelial cells, accompanied by enhanced leukocyte attachment. Preventing adipocyte derived EV-induced VCAM-1 upregulation may offer a novel therapeutic target in the prevention of obesity-driven cardiovascular disease.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesAtherosclerosis;
dc.titleInflammatory adipocyte-derived extracellular vesicles promote leukocyte attachment to vascular endothelial cellsen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1016/j.atherosclerosis.2019.01.013
dcterms.dateAccepted2019-01-10
rioxxterms.funderCardiff Metropolitan Universityen_US
rioxxterms.identifier.projectCardiff Metropolian (Internal)en_US
rioxxterms.versionNAen_US
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
rioxxterms.licenseref.startdate2019-04-05
rioxxterms.freetoread.startdate2020-01-24
rioxxterms.funder.project37baf166-7129-4cd4-b6a1-507454d1372een_US


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