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dc.contributor.authorJovanovic, Aleksandra
dc.contributor.authorSudar-Milovanovic, Emina
dc.contributor.authorObradovic, Milan
dc.contributor.authorPitt, Samantha Jane
dc.contributor.authorStewart, Alan James
dc.contributor.authorZafirovic, Sonja
dc.contributor.authorStanimirovic, Julijana
dc.contributor.authorRadak, Djordje
dc.contributor.authorIsenovic, Esma R.
dc.identifier.citationJovanovic , A , Sudar-Milovanovic , E , Obradovic , M , Pitt , S J , Stewart , A J , Zafirovic , S , Stanimirovic , J , Radak , D & Isenovic , E R 2017 , ' Influence of a high-fat diet on cardiac iNOS in female rats ' , Current Vascular Pharmacology , vol. 15 , no. 5 , pp. 491-500 .
dc.identifier.otherPURE: 246457163
dc.identifier.otherPURE UUID: 135375a6-f857-43aa-b27b-565b80a6dc90
dc.identifier.otherPubMed: 27781956
dc.identifier.otherScopus: 85041327847
dc.identifier.otherORCID: /0000-0003-4580-1840/work/60195778
dc.identifier.otherORCID: /0000-0003-2257-1595/work/60196222
dc.identifier.otherWOS: 000407476700011
dc.description.abstractOverexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular (CV) disease. Several studies have reported that oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. In the present study, female Wistar rats were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. Gene and protein expression of iNOS were measured in heart tissue. HF diet-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF diet-fed rats. Expression of the p50 subunit of nuclear factor-κB (NFκB-p50) in heart lysate was increased by 77% (p<0.01) in HF diet-fed rats. Expression and phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) in control and HF diet-fed rats were also examined. Expression of Akt and ERK1/2 were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2/ in HF-fed rats. Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were examined and shown to be significantly reduced in HF diet-fed rats. Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.
dc.relation.ispartofCurrent Vascular Pharmacologyen
dc.rights© 2016, Bentham Science Publishers. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at /
dc.subjectCardiovascular diseaseen
dc.subjectInducible nitric oxide synthaseen
dc.subjectQH426 Geneticsen
dc.subjectRC Internal medicineen
dc.subjectRM Therapeutics. Pharmacologyen
dc.titleInfluence of a high-fat diet on cardiac iNOS in female ratsen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.description.statusPeer revieweden

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