Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells

Lin, Xiaolan; Hu, Huijun; Liu, Yuanbo; Hu, Xuemei; Fan, Xiaojuan; Zou, Wei‐Wen; Pan, Yongquan; Zhou, Wenzong; Peng, Min-Wen; Gu, Changjiang

doi:10.3892/ijmm.2017.2949

Cited by 52 publications

(40 citation statements)

References 28 publications

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“…that apigenin can influence lipid metabolism by activating PPARγ [51]. 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].…”

Section: Discussionmentioning

confidence: 99%

“…The disruption of cholesterol homeostasis can induce lipid deposition in macrophages, leading to the formation of macrophage-derived foam cells and progression of AS [6]. ATP binding cassette A1 (ABCA1) can alleviate excessive lipid accumulation via accelerating cellular cholesterol efflux, which promotes macrophage reverse cholesterol transport (RCT) and high-density lipoproteins (HDL) formation.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…A growing body of evidence suggests that high density lipoprotein (HDL) plays an important role in the removal of cholesterol from atherosclerotic plaques and the transport of excess cholesterol back to the liver, and this is one of the main mechanisms to prevent the occurrence of AS, which called reverse cholesterol transport (RCT) [7][8][9]. ATP binding cassettes (ABC) A1 and G1 are key genes in RCT process [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Similar to ABCA1, ABCG1 plays a synergistic role in mediating cholesterol efflux to HDL and further exerts anti-AS effects [13]. However, acyl coenzyme a-cholesterol acyltransferase (ACAT) plays an important role in the absorption, transportation, and storage of cholesterol and is one of the key proteins that regulate the balance of cholesterol metabolism in the body [8,14]. In addition, during the formation of foam cells, members of the scavenger receptor family such as scavenger receptor-A1 (SR-A1) and CD36 mediate the sustained uptake of oxidized low density lipoprotein (ox-LDL) [15].…”

Section: Introductionmentioning

confidence: 99%

Recombinant Klotho protein enhances cholesterol efflux of THP-1 macrophage-derived foam cells via suppressing Wnt/β-catenin signaling pathway

Liu

Chen

et al. 2020

BMC Cardiovasc Disord

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Background: Atherosclerosis (AS) is the basis of cardiovascular diseases, characterized by chronic inflammatory and lipid metabolism disorders. Although the anti-inflammatory effect of Klotho in AS has been clearly shown, its lipidlowering effect is unclear. In this study, we examined the effects of recombinant Klotho (Re-KL) protein on lipid accumulation in foam cells. Methods: THP-1 cells were exposed to 100 nM phorbol myristate acetate for 24 h and then to oxidized low-density lipoprotein (ox-LDL; 80 mg/mL) to induce foam cell formation. Subsequently, the foam cells were incubated with Re-KL and/or DKK1, an inhibitor of the Wnt/β-catenin pathway. Results: Oil red O staining and cholesterol intake assay revealed that the foam cell model was constructed successfully. Pretreatment of the foam cells with Re-KL decreased total cholesterol level, up-regulated the expression of ATP binding cassette transporter A1 (ABCA1) and G1 (ABCG1), and down-regulated the expression of acyl coenzyme a-cholesterol acyltransferase 1 (ACAT1) and members of the scavenger family (SR-A1 and CD36). In addition, the expression of Wnt/β-catenin pathwayrelated proteins in foam cells was significantly decreased by the stimulus of Re-KL. Interestingly, the effect of Re-KL was similar to that of DKK1 on foam cells. Conclusions: The Re-KL-induced up-regulation of reverse cholesterol transport capacity promotes cholesterol efflux and reduces lipid accumulation by suppressing the Wnt/β-catenin pathway in foam cells.

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“…*p < .05 indicates significant difference expression and transcriptional activity. The uptake of oxLDL activates the transcription factor NFκB, whereas PMA activates Akt signaling pathway and upregulates NFκB transcriptional activity, which is the downstreaming pathway of Akt phosphorylation(Lin et al, 2017).…”

mentioning

confidence: 99%

Tithonia diversifolia ‐derived orizabin suppresses cell adhesion, differentiation, and oxidized LDL accumulation by Akt signaling suppression via PTEN promotion in THP‐1 cells

et al. 2020

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As a Japanese folk medicine, Tithonia diversifolia is used for cardiovascular disease prevention and health maintenance. We isolated T. diversifolia‐derived orizabin based on the nitric oxide production inhibitory effect. This study aimed to consider orizabin as a novel functional compound with anti‐atherosclerotic activity. Orizabin significantly inhibited the adhesion of THP‐1 cells to human umbilical vein endothelial cells (HUVECs) and suppressed the mRNA expression of adhesion molecules in HUVECs. In Phorbol 12‐myristate 13‐acetate stimulated THP‐1 cells, orizabin suppressed macrophage differentiation, CD36 expression (1% at 10 μM), and NFκB transcriptional activity. Furthermore, orizabin suppressed oxidized low‐density lipoprotein (oxLDL) uptake in macrophages and the Akt phosphorylation. On the contrary, we revealed that phosphatidylinositol‐3,4,5‐trisphosphate 3‐phosphatase (PTEN) mRNA and protein expression were promoted significantly by orizabin (mRNA, 270‐fold at 10 μM). Our study presented the possibility that T. diversifolia‐derived orizabin is novel anti‐atherosclerotic compound via the suppression of Akt phosphorylation, and T. diversifolia may be effective as a new crop for vascular health maintenance. Practical applications In this study, the differentiation of monocytes was suppressed without any toxicity, it was obvious in the image, and the oxLDL uptake in monocytes was clearly suppressed by orizabin. Our findings presented that T. diversifolia‐derived compound orizabin specifically contributes to the promotion of PTEN expression and suppression of Akt signal in cells, and acts to suppress inflammation by suppression of NFκB transcriptional activity. As a component derived from food, it has a strong function and can be used to maintain the health for blood vessels. It is also a finding that deserves to expand production currently being carried out on a small scale. Furthermore, the promoting effect of PTEN known as a cancer suppressor in orizabin may result in further use for pharmaceuticals research. Orizabin can be safely used as a food‐derived compound for maintaining human health.

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Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells

Cited by 52 publications

References 28 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

Recombinant Klotho protein enhances cholesterol efflux of THP-1 macrophage-derived foam cells via suppressing Wnt/β-catenin signaling pathway

Tithonia diversifolia ‐derived orizabin suppresses cell adhesion, differentiation, and oxidized LDL accumulation by Akt signaling suppression via PTEN promotion in THP‐1 cells

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