Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies

Yang, Xinyu; Li, Yang; Li, Yanda; Ren, Xiaomeng; Zhang, Xiaoyu; Hu, Dan; Gao, Yonghong; Xing, Yanwei; Shang, Hongcai

doi:10.3389/fphys.2017.00600

Cited by 309 publications

(239 citation statements)

References 182 publications

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“…As PPARγ/LXRα pathway has been well demonstrated in the regulation of ABCA1 expression [6,52,53], this pathway may also be responsible for apigenin-induced up-regulation of ABCA1 expression and cholesterol efflux, which still warrants further investigation. In addition to lipid disorder, persistent and chronic inflammation within vessel walls also gives a great impetus to AS progression [54]. A large body of research has demonstrated that NF-κB and TLR-4 activities are closely associated with lipid metabolism, inflammation and progression of AS [55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Ren

Jiang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4’, 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE^-/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE^-/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE^-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation.

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Section: Discussionmentioning

confidence: 99%

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Ren

Jiang

Zhou

et al. 2018

Cell Physiol Biochem

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“…OS was suggested to drive this process through impairment of cellular organelle functions and structure (Table ). In particular, endoplasmic reticulum stress and mitochondrial destruction in vascular and immune cells contribute to atherosclerotic plaque progression by modulating cell apoptosis and lipid peroxidation (Battson, Lee, & Gentile, ; Yang et al, ). Hypercholesterolemia has also been shown to exert direct and indirect effects on myocardial function characterized by impaired cardiac performance and contractile dysfunction.…”

Section: Os and Atheroprogression In Hypercholesterolemiamentioning

confidence: 99%

Oxidative burden in familial hypercholesterolemia

Mollazadeh¹,

Carbone

Montecucco

et al. 2018

Journal Cellular Physiology

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Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low-density lipoprotein cholesterol (LDL-c). FH is characterized by accelerated development of atherosclerosis and represents the most frequent hereditary cause of premature coronary heart disease. Mutations of the LDL receptor gene are the genetic signature of FH, resulting in abnormal levels of circulating LDLs. Moreover, FH promotes the generation of reactive oxygen species (ROS) which is another key mechanism involved in atherosclerosis development and progression. The aim of this narrative review is to update the current knowledge on the pathophysiological mechanisms linking FH to ROS generation and their detrimental impact on atherosclerotic pathophysiology. With this purpose, we reviewed experimental and clinical data on the association between FH and OS and the functional role of OS as a promoter of inflammation and atherosclerosis. In this regard, oxidant species such as oxidized LDL, malondialdehyde, ROS, and isoprostanes emerged as leading mediators of the oxidative injury in FH. In conclusion, targeting oxidative stress may be a promising therapeutic strategy to reduce atherogenesis in patients with FH.

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“…Increased mitochondrial oxidative stress and generation of excessive ROS are associated with atherosclerosis in humans and correlate with the severity and progression of atherosclerosis (Yang et al, ). In addition, the production of free oxygen radicals has been shown to initiate oxidation of lipids and proteins that impact vascular SMC migration and expression of adhesion molecules in the endothelium (Yang et al, ). Oxidation of polyunsaturated fatty acids (PUFAs), for example, n‐3 and n‐6, generates highly reactive unsaturated hydroxyalkenals which form protein adducts with lipoproteins.…”

Section: Oxidative Stress Underlies Chronic Diseasementioning

confidence: 99%

Dietary antioxidants remodel DNA methylation patterns in chronic disease

Beetch

Harandi-Zadeh

Shen

et al. 2019

British J Pharmacology

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Chronic diseases account for over 60% of all deaths worldwide according to the World Health Organization reports. Majority of cases are triggered by environmental exposures that lead to aberrant changes in the epigenome, specifically, the DNA methylation patterns. These changes result in altered expression of gene networks and activity of signalling pathways. Dietary antioxidants, including catechins, flavonoids, anthocyanins, stilbenes and carotenoids, demonstrate benefits in the prevention and/or support of therapy in chronic diseases. This review provides a comprehensive discussion of potential epigenetic mechanisms of antioxidant compounds in reversing altered patterns of DNA methylation in chronic disease. Antioxidants remodel the DNA methylation patterns through multiple mechanisms, including regulation of epigenetic enzymes and chromatin remodelling complexes. These effects can further contribute to antioxidant properties of the compounds. On the other hand, decrease in oxidative stress itself can impact DNA methylation delivering additional link between antioxidant mechanisms and epigenetic effects of the compounds. Linked Articles This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc

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Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies

Cited by 309 publications

References 182 publications

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Oxidative burden in familial hypercholesterolemia

Dietary antioxidants remodel DNA methylation patterns in chronic disease

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