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Effects Of Vitamin E On Peroxisome Proliferator-activated Receptor γ And Nuclear Factor-erythroid 2-related Factor 2 In Hypercholesterolemia-induced Atherosclerosis.

Perinur Bozaykut, B. Karademir, Burak Yazgan, Erdi Sozen, R. Siow, G. Mann, N. Ozer
Published 2014 · Biology, Medicine

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Atherosclerosis 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 (50mg/kg). To elucidate the mechanisms by which vitamin E supplementation alters the effects of hypercholesterolemia in rabbit aortae, we measured peroxisome proliferator-activated receptor γ (PPARγ), 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 α (GSTα) protein by immunoblotting. The increased MMP-1 and decreased GSTα 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 PPARγ, GSTα, 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.
This paper references
Antioxidant gene therapy for cardiovascular disease: current status and future perspectives.
Anna-Liisa Levonen (2008)
NF-E2–Related Factor 2 Promotes Atherosclerosis by Effects on Plasma Lipoproteins and Cholesterol Transport That Overshadow Antioxidant Protection
B. Barajas (2011)
Detection of Superoxide in Vascular Tissue
T. Muenzel (2002)
Ellagic acid inhibits oxidized low-density lipoprotein (OxLDL)-induced metalloproteinase (MMP) expression by modulating the protein kinase C-α/extracellular signal-regulated kinase/peroxisome proliferator-activated receptor γ/nuclear factor-κB (PKC-α/ERK/PPAR-γ/NF-κB) signaling pathway in endothelia
Mei-ying Kuo (2011)
Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo.
Bao-Hong Lee (2012)
Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb
J. Jiang (1998)
Protective effects of vitamin E against hypercholesterolemia-induced age-related diseases
Betul Catalgol (2011)
Effect of vitamin E on the development of atherosclerosis.
N. Ozer (2000)
Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: a role for Nrf2 in vascular protection in diabetes.
M. He (2011)
Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro.
N. Marx (1998)
Keap1-dependent Proteasomal Degradation of Transcription Factor Nrf2 Contributes to the Negative Regulation of Antioxidant Response Element-driven Gene Expression*
M. McMahon (2003)
Expression of rat liver glutathione-S-transferase GSTA5 in cell lines provides increased resistance to alkylating agents and toxic aldehydes.
Shubana Kazi (2002)
Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation
N. Wakabayashi (2003)
Nrf2, a PPARγ Alternative Pathway to Promote CD36 Expression on Inflammatory Macrophages: Implication for Malaria
David Olagnier (2011)
Cellular, molecular and clinical aspects of vitamin E on atherosclerosis prevention.
A. Munteanu (2007)
A PPARγ-LXR-ABCA1 Pathway in Macrophages Is Involved in Cholesterol Efflux and Atherogenesis
Ajay Chawla (2001)
Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway.
Xinghua Cheng (2011)
Vitamin E supplement use and the incidence of cardiovascular disease and all-cause mortality in the Framingham Heart Study: Does the underlying health status play a role?
M. Dietrich (2009)
Reactive oxygen species activate focal adhesion kinase, paxillin and p130cas tyrosine phosphorylation in endothelial cells.
A. Gozin (1998)
Peroxisome proliferator–activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor–deficient mice
A. Li (2000)
Peroxisome proliferator-activated receptor-gamma ligands regulate endothelial membrane superoxide production.
Jinah Hwang (2005)
Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system.
T. Kim (2013)
On the mechanism for PPAR agonists to enhance ABCA1 gene expression.
M. Ogata (2009)
Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages*
T. Ishii (2000)
Glutathione-S-transferase A4-4 modulates oxidative stress in endothelium: possible role in human atherosclerosis. Atherosclerosis
Y. Yang (2004)
Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger receptor expression in cultured aortic smooth muscle cells.
R. Ricciarelli (2000)
Disruption of Nrf2, a Key Inducer of Antioxidant Defenses, Attenuates ApoE-Mediated Atherosclerosis in Mice
T. Sussan (2008)
Foam cells in atherosclerosis.
Xiao-hua Yu (2013)
Role of Nrf2 in the Regulation of CD36 and Stress Protein Expression in Murine Macrophages: Activation by Oxidatively Modified LDL and 4-Hydroxynonenal
Tetsuro Ishii (2004)
Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits.
N. Ozer (1998)
Vitamin E: non-antioxidant roles.
A. Azzi (2000)
Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic rabbits.
N. Ozer (2006)
Effect of vitamin E on human aortic endothelial cell production of chemokines and adhesion to monocytes.
D. Wu (1999)
Involvement of glutathione/glutathione S‐transferase antioxidant system in butyrate‐inhibited vascular smooth muscle cell proliferation
K. Ranganna (2007)
The Antioxidant Defense System Keap1-Nrf2 Comprises a Multiple Sensing Mechanism for Responding to a Wide Range of Chemical Compounds
M. Kobayashi (2008)
Atherosclerosis--an inflammatory disease.
R. Ross (1999)
Enhanced CD36 expression changes the role of Nrf2 activation from anti-atherogenic to pro-atherogenic in apoE-deficient mice.
Hirotaka Sawada (2012)
Peroxisome Proliferator-activated Receptor-γ Down-regulates Chondrocyte Matrix Metalloproteinase-1 via a Novel Composite Element*
M. François (2004)
Targeting the Nrf2–Keap1 antioxidant defence pathway for neurovascular protection in stroke
A. Alfieri (2011)
Retinoid X receptor and peroxisome proliferator-activated receptor-gamma agonists cooperate to inhibit matrix metalloproteinase gene expression
P. Burrage (2008)
Contribution of oxidative stress to pulmonary arterial hypertension.
V. DeMarco (2010)
PPAR-γ Ligands Repress TGFβ-Induced Myofibroblast Differentiation by Targeting the PI3K/Akt Pathway: Implications for Therapy of Fibrosis
A. Kulkarni (2011)
Modulation of NO and ROS production by AdiNOS transduced vascular cells through supplementation with L-Arg and BH4: implications for gene therapy of restenosis.
Scott P. Forbes (2013)
Increased expression of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma in human atherosclerosis.
Sumihisa Sueyoshi (2010)
PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines.
C. Jiang (1998)
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
A. Dinkova-Kostova (2002)
upregulation in hyperglycemia-activated endothelial cells
Clintoria R Williams (2016)
Transfection of mGSTA4 in HL-60 cells protects against 4-hydroxynonenal-induced apoptosis by inhibiting JNK-mediated signaling.
J. Cheng (2001)
Synergistic effect of cyanidin and PPAR agonist against nonalcoholic steatohepatitis-mediated oxidative stress-induced cytotoxicity through MAPK and Nrf2 transduction pathways.
Ping-Hsiao Shih (2012)
Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice.
A. Li (2000)
Vitamin E supplement use and the incidence of cardiovascular disease and allcause mortality in the Framingham Heart Study: does the underlying health status play a role? Atherosclerosis
M. Dietrich (2009)
Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs.
T. Satoh (2013)
Glutathione-S-transferase A4-4 modulates oxidative stress in endothelium: possible role in human atherosclerosis.
Y. Yang (2004)
Homocysteine induces DNA synthesis and proliferation of vascular smooth muscle cells by a hydrogen peroxide-independent mechanism.
S. Taha (1999)
Oxidized Low-Density Lipoprotein Induces Apoptosis in Endothelial Progenitor Cells by Inactivating the Phosphoinositide 3-Kinase/Akt Pathway
G. Tie (2010)
Enhanced CD 36 expression changes the role of Nrf 2 activation from anti - atherogenic to pro - atherogenic in apoE - de fi cient mice
H. Sawada (2012)
Macrophages in Human Atheroma Contain PPARγ: Differentiation-Dependent Peroxisomal Proliferator-Activated Receptor γ (PPARγ) Expression and Reduction of MMP-9 Activity through PPARγ Activation in Mononuclear Phagocytes in Vitro
N. Marx (1998)
Antagonistic effects of oxidized low density lipoprotein and alpha-tocopherol on CD36 scavenger receptor expression in monocytes: involvement of protein kinase B and peroxisome proliferator-activated receptor-gamma.
Adelina Munteanu (2006)
A method for determining concentrations of retinol, tocopherol, and five carotenoids in human plasma and tissue samples.
D. Nierenberg (1992)
Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differentiation.
Seungha Hyeon (2013)
Glutathione - S - transferase A 4 - 4 modulates oxidative stress in endothelium : possible role in human
K. Ranganna
A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.
A. Chawla (2001)
Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease☆
S. Chapple (2013)
Effect of vitamin E on human aortic endothelial cell production of chemokines and adhesion to monocytes. Atherosclerosis
D. Wu (1999)
Modulation of NO and ROS production by AdiNOS transduced vascular cells through supplementation with L-Arg and BH4: ımplications for gene therapy of restenosis. Atherosclerosis
S. P. Forbes (2013)

This paper is referenced by
The effects of magnesium and vitamin E co-supplementation on parameters of glucose homeostasis and lipid profiles in patients with gestational diabetes
Maryam Maktabi (2018)
Synthesis and characterization of hyaluronic acid coated manganese dioxide microparticles that act as ROS scavengers.
J. Bizeau (2017)
The Relationship between Environmental Tobacco Smoke Exposure and Cardiovascular Disease and the Potential Modifying Effect of Diet in a Prospective Cohort among American Indians: The Strong Heart Study
S. Rajkumar (2017)
Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones
Diana Alemán-González-Duhart (2016)
Mitochondria and cardiovascular diseases-from pathophysiology to treatment.
G. Siasos (2018)
Molecular Understanding of the Cardiomodulation in Myocardial Infarction and the Mechanism of Vitamin E Protection.
Khairul Anwar Zarkasi (2019)
Vitamin E Conditionally Inhibits Atherosclerosis in ApoE Knockout Mice by Anti-oxidation and Regulation of Vasculature Gene Expressions
F. Tang (2014)
An excess dietary vitamin E concentration does not influence Nrf2 signaling in the liver of rats fed either soybean oil or salmon oil
K. Eder (2017)
Chronic stress: a crucial promoter of cell apoptosis in atherosclerosis
L. Meng (2019)
The effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome.
M. Jamilian (2018)
High Cholesterol Diet-Induced Changes in Oxysterol and Scavenger Receptor Levels in Heart Tissue
Erdi Sozen (2018)
Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain
R. Marinelli (2020)
Vitamin E alleviates phoxim-induced toxic effects on intestinal oxidative stress, barrier function, and morphological changes in rats
Y. Sun (2018)
A Mitochondrial Approach to Cardiovascular Risk and Disease.
C. Veloso (2019)
Vitamin E promotes ovine Sertoli cell proliferation by regulation of genes associated with cell division and the cell cycle.
Yuefeng Gao (2020)
Antioxidant alterations link polycyclic aromatic hydrocarbons to blood pressure in children.
Q. Wang (2020)
Impact of natural products on the cholesterol transporter ABCA1.
Dongdong Wang (2019)
Vitamin E: Regulatory Role on Signal Transduction
J. Zingg (2019)
The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review).
Hawa Nordin Siti (2015)
Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature: from increased cellular senescence to the pathogenesis of age-related vascular diseases
Z. Ungvari (2019)
Assessment of Serum Nitrogen Species and Inflammatory Parameters in Relapsing-Remitting Multiple Sclerosis Patients Treated with Different Therapeutic Approaches
N. Niedziela (2016)
Naturally Occurring Compounds: New Potential Weapons against Oxidative Stress in Chronic Kidney Disease
L. Signorini (2017)
Aβ and tau toxicities in Alzheimer’s are linked via oxidative stress-induced p38 activation: Protective role of vitamin E
E. Giraldo (2014)
Sodium–glucose cotransporter inhibitors and oxidative stress: An update
H. Yaribeygi (2019)
FGF21 deletion exacerbates diabetic cardiomyopathy by aggravating cardiac lipid accumulation
Xiaoqing Yan (2015)
Vitamin E: A Role in Signal Transduction.
J. Zingg (2015)
Long-Term Vitamin E-Deficient Mice Exhibit Cognitive Dysfunction via Elevation of Brain Oxidation.
K. Fukui (2015)
The effect of tocotrienol-rich fraction on the expression of glutathione S-transferase isoenzymes in mice liver
Ahmed Atia (2018)
Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic steatohepatitis
Perinur Bozaykut (2016)
Collaborative Power of Nrf2 and PPARγ Activators against Metabolic and Drug-Induced Oxidative Injury
Choongho Lee (2017)
ABCG1 is involved in vitamin E efflux.
M. Olivier (2014)
Vitamin E: Emerging aspects and new directions
F. Galli (2017)
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