• Proceedings of the PSK Conference
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• 2003.04a
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• pp.141.2-141.2
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• 2003

Subendothelial accumulation of foam cells plays a key role in the initiation of atherosclerosis. These foam cells accumulate in fatty streaks that evolve to more complex fibrofatty or atheromatous plaques. Oxidized LDL may also be involved in atherogenesis by inducing smooth muscle cell proliferation and smooth muscle foam cell generation. (omitted)

• Journal of Microbiology and Biotechnology
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• v.32 no.11
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• pp.1406-1415
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• 2022

The formation of macrophage foam cells stimulated by oxidized low-density lipoprotein (ox-LDL) is deemed an important cause of atherosclerosis. Transcription factor Yin Yang 1 (YY1), which is a universally expressed multifunctional protein, is closely related to cell metabolism disorders such as lipid metabolism, sugar metabolism, and bile acid metabolism. However, whether YY1 is involved in macrophage inflammation and lipid accumulation still remains unknown. After mouse macrophage cell line RAW264.7 cells were induced by ox-LDL, YY1 and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions were found to be increased while low-density lipoprotein receptor (LDLR) expression was lowly expressed. Subsequently, through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, Oil Red O staining and cholesterol quantification, it turned out that silencing of YY1 attenuated the inflammatory response and lipid accumulation in RAW264.7 cells caused by ox-LDL. Moreover, results from the JASPAR database, chromatin immunoprecipitation (ChIP) assay, luciferase reporter assay and Western blot analysis suggested that YY1 activated PCSK9 by binding to PCSK9 promoter and modulated the expression of LDLR in the downstream of PCSK9. In addition, the results of functional experiments demonstrated that the inhibitory effects of YY1 interference on ox-LDL-mediated macrophage inflammation and lipid accumulation were reversed by PCSK9 overexpression. To sum up, YY1 depletion inhibited its activation of PCSK9, thereby reducing cellular inflammatory response, cholesterol homeostasis imbalance, and lipid accumulation caused by ox-LDL.

• Molecules and Cells
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• v.28 no.3
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• pp.175-181
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• 2009

In hypertriglyceridaemic individuals, atherosclerogenesis is associated with the increased concentrations of very low density lipoprotein (VLDL) and VLDL-associated remnant particles. In vitro studies have suggested that VLDL induces foam cells formation. To reveal the changes of the proteins expression in the process of foam cells formation induced by VLDL, we performed a proteomic analysis of the foam cells based on the stimulation of differentiated THP-1 cells with VLDL. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, 14 differentially expressed proteins, containing 8 up-regulated proteins and 6 down-regulated proteins were identified. The proteins are involved in energy metabolism, oxidative stress, cell growth, differentiation and apoptosis, such as adipose differentiation-related protein (ADRP), enolase, S100A11, heat shock protein 27 and so on. In addition, the expression of some selected proteins was confirmed by Western blot and RT-PCR analysis. The results suggest that VLDL not only induces lipid accumulation, but also brings about foam cells diverse characteristics by altering the expression of various proteins.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.121-129
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• 2018

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.

• Korean Journal of Food Science and Technology
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• v.39 no.2
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• pp.181-188
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• 2007

This study examined the effects of green tea extract supplementation (500 or 1,000 mg/kg b.w. per day) in conjunction with an atherogenic diet (10% coconut oil (w/w), 0.1% cholesterol) on plasma lipid composition, regression of pre-existing foam cells, and on the mRNA levels of hepatic HMG-CoA reductase and LDL receptor. Compared to groups fed only with the atherogenic diet, the addition of green tea extract to atherogenic diet-fed groups significantly down-regulated plasma triglyceride and total cholesterol levels, dose-dependently. Supplementation of 1,000 mg/kg b.w. of green tea extract with the atherogenic diet induced significant up-regulation of both HMG-CoA reductase and LDL receptor messenger RNA levels in liver as compared to the group receiving green tea extract supplementation at 500 mg/kg b.w. The F1B hamsters fed the atherogenic diet had greater foam cell accumulation compared to those fed a normal diet, or the atherogenic diet supplemented with green tea extract. Regression of fatty streak lesions was achieved by atherosclerosis in fat- and cholesterol-fed hamsters and this effect was associated with down-regulation of plasma cholesterol and up-regulation of hepatic LDL receptor expression.

• BMB Reports
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• v.57 no.2
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• pp.92-97
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• 2024

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis.

• Korean Journal of Food Science and Technology
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• v.37 no.6
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• pp.962-969
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• 2005

Effects of 5 and 10% dietary supplement tablets containing green tea, buckwheat, and grape leaf extracts on atherosclerosis, and plasma and hepatic lipid compositions in hamsters fed antherogenic diet [modified AIN-76A containing 10% coconut oil (w/w), 0.05% cholesterol] were examined. Compared to atherogenic diet only groups, addition of supplement to atherogenic diet-fed group significantly down-regulated triglyceride and total cholesterol levels in plasma and liver. F1B hamsters fed atherogenic diet had greater foam cell accumulation compared to control and those fed atherogenic diet with addition of supplement. Lipid metabolisms of plasma and liver increased with addition of supplement dose-dependently, whereas aortic lipid accumulation decreased. These results indicate tablets supplemented with green tea, buckwheat, and grape leaf extracts have potential to prevent cardiovascular diseases in golden Syrian hamsters.

• Korean Journal of Plant Resources
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• v.23 no.6
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• pp.519-525
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• 2010

Chlorogenic acid, formed of an ester of caffeic acid and quinic acid, which is naturally abundant in many plant species, was used as a model O-dihydoxy phenolic compound. In the previous study, we have reported that the isolated constituent from Apocynum venetum leaves has an inhibitory effect on $Cu^{2+}$-induced oxidative modification of low-density lipoprotein (LDL). Among them, chlorogenic acid showed the most potent anti-LDL oxidative activity than other compounds. For the reason, we investigated the inhibitory effect of the chlorogenic acid on $Cu^{2+}$-induced oxidative modification of LDL, monitored a lag time in the conjugated-diene formation and TBARS formation, and measured TNBS free amino acid group, and form cell formation in vitro system. The TBARS- and diene- formation were strongly inhibited by chlorogenic acid ($0{\sim}100\;{\mu}g/ml$) with dose dependent manner. On the other hand, TNBS reactive lysine amino groups on LDL oxidation were protected by chlorogenic acid- treated cell group. Therefore, chlorogenic acid inhibited to cholesterol accumulation in the isolated peritoneal macrophage.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.22-31
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• 2021

Atherosclerosis (AS) is a leading cause of cardiovascular diseases (CVDs) and it results in a high rate of death worldwide, with an increased prevalence with age despite advances in lifestyle management and drug therapy. Atherosclerosis is a chronic progressive inflammatory process, and it mainly presents with lipid accumulation, foam cell proliferation, inflammatory response, atherosclerotic plaque formation and rupture, thrombosis, and vascular calcification. Therefore, there is a great need for reliable therapeutic drugs or remedies to cure or alleviate atherosclerosis and reduce the societal burden. Ginsenosides are natural steroid glycosides and triterpene saponins obtained mainly from the plant ginseng. Several recent studies have reported that ginsenosides have a variety of pharmacological activities against several diseases including inflammation, cancer and cardiovascular diseases. This review focuses on describing the different pharmacological functions and underlying mechanisms of various active ginsenosides (Rb1,-Rd, -F, -Rg1, -Rg2, and -Rg3, and compound K) for atherosclerosis, which could provide useful insights for developing novel and effective anti-cardiovascular drugs.