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dc.contributor.authorHierons, Stephen J.
dc.contributor.authorMarsh, Jordan S.
dc.contributor.authorWu, Dongmei
dc.contributor.authorBlindauer, Claudia A.
dc.contributor.authorStewart, Alan J.
dc.date.accessioned2021-09-20T14:30:08Z
dc.date.available2021-09-20T14:30:08Z
dc.date.issued2021-09-20
dc.identifier.citationHierons , S J , Marsh , J S , Wu , D , Blindauer , C A & Stewart , A J 2021 , ' The interplay between non-esterified fatty acids and plasma zinc and its influence on thrombotic risk in obesity and type 2 diabetes ' , International Journal of Molecular Sciences , vol. 22 , no. 18 , 10140 . https://doi.org/10.3390/ijms221810140en
dc.identifier.issn1422-0067
dc.identifier.otherPURE: 275899949
dc.identifier.otherPURE UUID: 2fefd635-f01b-4496-a86a-d6844f26bf52
dc.identifier.urihttp://hdl.handle.net/10023/23991
dc.descriptionThis work is funded by the British Heart Foundation (grant numbers: FS/20/3/34956 and FS/19/69/34639), the China Scholarship Council and the Leverhulme Trust (grant number: RPG-2017-214).en
dc.description.abstractThrombosis is a major comorbidity of obesity and type-2 diabetes mellitus (T2DM). Despite the development of numerous effective treatments and preventative strategies to address thrombotic disease in such individuals, the incidence of thrombotic complications remains high. This suggests that not all the pathophysiological mechanisms underlying these events have been identified or targeted. Non-esterified fatty acids (NEFAs) are increasingly regarded as a nexus between obesity, insulin resistance and vascular disease. Notably, plasma NEFA levels are consistently elevated in obesity and T2DM and may impact haemostasis in several ways. A potentially unrecognised route of NEFA-mediated thrombotic activity is their ability to disturb Zn2+ speciation in the plasma. Zn2+ is a potent regulator of coagulation and its availability in the plasma is monitored carefully through buffering by human serum albumin (HSA). The binding of long-chain NEFAs such as palmitate and stearate however trigger a conformational change in HSA that reduce its ability to bind Zn2+ thus increasing the ion’s availability to bind and activate coagulation proteins. NE-FA-mediated perturbation of HSA-Zn2+ binding is thus predicted to contribute to the prothrom-botic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders.
dc.format.extent17
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciencesen
dc.rightsCopyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectDiabetesen
dc.subjectHuman serum albuminen
dc.subjectInsulin resistanceen
dc.subjectNon-esterified fatty acidsen
dc.subjectObesityen
dc.subjectThrombosisen
dc.subjectZincen
dc.subjectQH301 Biologyen
dc.subject.lccQH301en
dc.titleThe interplay between non-esterified fatty acids and plasma zinc and its influence on thrombotic risk in obesity and type 2 diabetesen
dc.typeJournal itemen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.3390/ijms221810140
dc.description.statusPeer revieweden
dc.identifier.urlhttps://www.mdpi.com/1422-0067/22/18/10140en


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