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Fenofibrate protects endothelial cells against the harmful effects of TNF-alpha

dc.contributor.authorWestcott, Corlien_ZA
dc.contributor.authorGenis, Amandaen_ZA
dc.contributor.authorMthethwa, Mashuduen_ZA
dc.contributor.authorGraham, Roxanneen_ZA
dc.contributor.authorVan Vuuren, Dericken_ZA
dc.contributor.authorHuisamen, Barbaraen_ZA
dc.contributor.authorStrijdom, Hansen_ZA
dc.date.accessioned2017-04-06T07:00:46Z
dc.date.available2017-04-06T07:00:46Z
dc.date.issued2017
dc.identifier.citationWestcott, C. et al. 2017. Fenofibrate protects endothelial cells against the harmful effects of TNF-alpha. SA Heart, 14(1):22-34, doi:10.24170/14-1-1865.
dc.identifier.issn2071-4602 (online)
dc.identifier.issn1996-6741 (print)
dc.identifier.otherdoi:10.24170/14-1-1865
dc.identifier.urihttp://hdl.handle.net/10019.1/101496
dc.descriptionCITATION: Westcott, C. et al. 2017. Fenofibrate protects endothelial cells against the harmful effects of TNF-alpha. SA Heart, 14(1):22-34, doi:10.24170/14-1-1865.
dc.descriptionThe original publication is available at http://www.journals.ac.za/index.php/SAHJ
dc.description.abstractIntroduction: Fenofibrate exerts pleiotropic effects on endothelial cells (ECs) by, amongst others, increasing nitric oxide (NO) production. We aimed to investigate fenofi brate’s putative beneficial actions in healthy or TNF-alpha-induced dysfunctional ECs. Methods: Fenofi brate-induced pro-vasodilatory responses were assessed in aortic rings (50 - 125μM; 30min) with and without L-NMMA (100μM). Rat cardiac microvascular ECs were treated with fenofibrate (30 and 50μM; 1h). In the pre-treatment experiments, fenofibrate (50μM) was administered one hour before TNFalpha treatment (20ng/ml; 24h). NO-production (DAF-2/DA or Griess assay), mitochondrial ROS-production (MitoSox™), cell viability (propidium iodide staining), and changes in the expression/phosphorylation of critical endothelial proteins were measured by Western blotting. Results: Fenofibrate increased NO-production ˜2-fold in healthy ECs (p<0.05 vs. vehicle). A ˜23% pro-vasodilatory response was induced in aortic rings, which was reversed by L-NMMA (p<0.05 vs. fenofibrate). Fenofibrate pretreatment ameliorated TNF-alpha-induced endothelial dysfunction by reversing the loss of NO, improving oxidative stress, restoring cell viability and preventing caspase-3 activation. Protective effects were underpinned by ˜47% and ˜49% up-regulation of activated eNOS and AMP-kinase, respectively (p<0.05 vs. TNFalpha). Conclusions: Fenofibrate protects TNF-alpha-induced dysfunctional ECs via up-regulated eNOS-NO, reduced oxidative stress and improved cell viability. These novel findings warrant further investigations to explore the potential use of fenofibrate as an anti-endothelial dysfunction therapeutic agent.en_ZA
dc.description.urihttp://www.journals.ac.za/index.php/SAHJ/article/view/1865
dc.format.extent13 pages
dc.language.isoen_ZAen_ZA
dc.publisherSouth African Heart Association
dc.subjectFenofibrateen_ZA
dc.subjectEndothelial dysfunctionen_ZA
dc.subjectNitric oxideen_ZA
dc.subjectTNF-alphaen_ZA
dc.titleFenofibrate protects endothelial cells against the harmful effects of TNF-alphaen_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's version
dc.rights.holderAuthors retain copyright


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