• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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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)

• IMMUNE NETWORK
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• 제20권3호
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• pp.22.1-22.21
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• 2020

In the progression of atherosclerosis, macrophages are the key immune cells for foam cell formation. During hyperlipidemic condition, phagocytic cells such as monocytes and macrophages uptake oxidized low-density lipoproteins (oxLDLs) accumulated in subintimal space, and lipid droplets are accumulated in their cytosols. In this review, we discussed the characteristics and phenotypic changes of macrophages in atherosclerosis and the effect of cytosolic lipid accumulation on macrophage phenotype. Due to macrophage plasticity, the inflammatory phenotypes triggered by oxLDL can be re-programmed by cytosolic lipid accumulation, showing downregulation of NF-κB activation followed by activation of anti-inflammatory genes, leading to tissue repair and homeostasis. We also discuss about various in vivo and in vitro models for atherosclerosis research and next generation sequencing technologies for foam cell gene expression profiling. Analysis of the phenotypic changes of macrophages during the progression of atherosclerosis with adequate approach may lead to exact understandings of the cellular mechanisms and hint therapeutic targets for the treatment of atherosclerosis.

• Journal of Microbiology and Biotechnology
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• 제32권11호
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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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• 제28권3호
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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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• 제26권2호
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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.

• 한국식품과학회지
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• 제39권2호
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• pp.181-188
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• 2007

8주령의 F1B golden Syrian 햄스터에게 동맥경화 유발식이와 함께 녹차 추출물을 각각 500 혹은 1,000 mg/kg b.w.의 양을 매일 경구투여하면서 6주간 사육하였을 때 햄스터 체내의 지질대사와 대동맥 내에서의 지방의 축적 정도에 미치는 영향을 조사하였다. 실험 결과 녹차추출물의 경구투여는 동맥경화유발식이를 섭취하는 햄스터의 혈중 중성지방과 총콜레스테롤치를 농도의존적으로 감소시켰고, 대동맥궁내에서의 지방의 축적을 예방하였다. 특히 녹차추출물 1,000 mg/kg b.w. 투여는 동맥경화유발식이를 섭취한 햄스터에서 간장내의 LDL receptor mRNA level을 증가시키는 경향을 보였다. 이러한 결과로 볼 때 녹차 추출물의 투여는 동맥경화유발식이를 섭취한 햄스터의 혈중 콜레스테롤치를 감소시키고 LDL receptor의 발현을 증가시킴으로써 동맥경화를 예방할 수 있음을 보여주었다.

• BMB Reports
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• 제57권2호
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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.

• 한국식품과학회지
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• 제37권6호
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• pp.962-969
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• 2005

7주령의 F1B golden Syrian 햄스터에게 동맥경화 유발식이에 녹차추출물, 메밀추출물 및 포도잎 추출물을 함유한 타블렛 제품을 각각 5%와 10%로 첨가하여 7주간 사육하였을 때 햄스터 체내의 지질성분과 대동맥 내에서의 지방의 축적 정도에 미치는 영향을 조사하였다. 실험 결과 녹차, 메밀, 포도잎 추출물을 함유한 타블렛 제품은 동맥경화유발식이를 섭취하는 햄스터의 혈중 중성지방과 총콜레스테롤치를 감소시켰고, 대동맥궁내에서의 지방의 축적을 예방하였고, 간장내 중성지방과 총콜레스테롤치를 감소시키는 것으로 나타났다. 특히 5%를 첨가한 군보다 10%를 첨가한 군에서 더 높은 효과를 나타내어 농도 의존적인 경향을 보였다. 이러한 결과를 통해 녹차, 메밀 및 포도잎 추출물 분말을 이용하여 식이 보조제의 형태로 개발한 타블렛 제품이 동맥경화를 예방하는 식품으로써 효과가 있음을 확인할 수 있었다.

• 한국자원식물학회지
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• 제23권6호
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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.