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Effects of vitamin E on peroxisome proliferator-activated receptor gamma and nuclear factor-erythroid 2-related factor 2 in hypercholesterolemia-induced atherosclerosis

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dc.contributor.authorSÖZEN, AHMET ERDİ
dc.contributor.authorsBozaykut, Perinur; Karademir, Betul; Yazgan, Burak; Sozen, Erdi; Siow, Richard C. M.; Mann, Giovanni E.; Ozer, Nesrin Kartal
dc.date.accessioned2022-03-13T12:45:58Z
dc.date.available2022-03-13T12:45:58Z
dc.date.issued2014
dc.description.abstractAtherosclerosis and associated cardiovascular complications such as stroke and myocardial infarction are major causes of morbidity and mortality. We have previously reported a significant increase in mRNA levels of the scavenger receptor CD36 in aortae of cholesterol-fed rabbits and shown that vitamin E treatment attenuated increased CD36 mRNA expression. In the present study, we further investigated the redox signaling pathways associated with protection against atherogenesis induced by high dietary cholesterol and correlated these with CD36 expression and the effects of vitamin E supplementation in a rabbit model. Male albino rabbits were assigned to either a control group fed with a low vitamin E diet alone or a test group fed with a low vitamin E diet containing 2% cholesterol in the absence or presence of daily intramuscular injections of vitamin E (50 mg/kg). To elucidate the mechanisms by which vitamin E supplementation alters the effects of hypercholesterolemia in rabbit aortae, we measured peroxisome proliferator-activated receptor gamma (PPAR gamma), ATP-binding cassette transporter A1 (ABCA1), and matrix metalloproteinase-1 (MMP-1) mRNA levels by quantitative RT-PCR and the expression of MMP-1, nuclear factor-erythroid 2-related factor 2 (Nrf2), and glutathione S-transferase alpha (GST alpha) protein by immunoblotting. The increased MMP-1 and decreased GSTa expression observed suggests that a cholesterol-rich diet contributes to the development of atherosclerosis, whereas vitamin E supplementation affords protection by decreasing MMP-1 and increasing PPAR gamma, GSTa, and ABCA1 levels in aortae of rabbits fed a cholesterol-rich diet. Notably, protein expression of Nrf2, the antioxidant transcription factor, was increased in both the cholesterol-fed and the vitamin E-supplemented groups. Although Nrf2 activation can promote CD36-mediated cholesterol uptake by macrophages, the increased induction of Nrf2-mediated antioxidant genes is likely to contribute to decreased lesion progression. Thus, our study demonstrates that Nrf2 can mediate both pro- and antiatherosclerotic effects. (C) 2014 Elsevier Inc. All rights reserved.
dc.identifier.doi10.1016/j.freeradbiomed.2014.02.017
dc.identifier.eissn1873-4596
dc.identifier.issn0891-5849
dc.identifier.pubmed24583459
dc.identifier.urihttps://hdl.handle.net/11424/237874
dc.identifier.wosWOS:000335487100017
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INC
dc.relation.ispartofFREE RADICAL BIOLOGY AND MEDICINE
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAtherosclerosis
dc.subjectHypercholesterolemia
dc.subjectNrf2
dc.subjectPPAR gamma
dc.subjectRedox signaling
dc.subjectVitamin E
dc.subjectFree radicals
dc.subjectLOW-DENSITY-LIPOPROTEIN
dc.subjectSMOOTH-MUSCLE-CELLS
dc.subjectENDOTHELIAL-CELLS
dc.subjectOXIDATIVE STRESS
dc.subjectGENE-EXPRESSION
dc.subjectPPAR-GAMMA
dc.subjectCARDIOVASCULAR-DISEASE
dc.subjectDEFENSE PATHWAY
dc.subjectNRF2 ACTIVATION
dc.subjectDEFICIENT MICE
dc.titleEffects of vitamin E on peroxisome proliferator-activated receptor gamma and nuclear factor-erythroid 2-related factor 2 in hypercholesterolemia-induced atherosclerosis
dc.typearticle
dspace.entity.typePublication
local.avesis.idc20a19a0-a36c-4f9d-aa2f-84efeff394ed
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages8
oaire.citation.endPage181
oaire.citation.startPage174
oaire.citation.titleFREE RADICAL BIOLOGY AND MEDICINE
oaire.citation.volume70
relation.isAuthorOfPublication47991a21-cce9-4b87-b091-bede64f8b4e0
relation.isAuthorOfPublication.latestForDiscovery47991a21-cce9-4b87-b091-bede64f8b4e0

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