• 대한의생명과학회지
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• 제9권3호
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• pp.123-131
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• 2003

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study hypothesized that a vascular infection with cytomegalovirus (CMV) may induce a chronic inflammatory reaction and activated inflammatory cells may express inflammatory mediators such as cyclooxygenase-2 (COX-2) and matrix metalloproteinases-9 (MMP-9). To confirm the hypothesis, the immunohistochemical stains for CMV late antigen, COX-2, MMP-9, macrophage, and T-lymphocyte were performed on CMV-infected atherosclerotic lesions. The immunoreactivity for COX-2 and MMP-9 was evident in all cases of atherosclerosis along with plaques, mainly in macrophages/foamy cells, intimal and medial smooth muscle cells, and endothelial cells of the intima. Within the intima, the increased immunoreactivity for COX-2 and MMP-9 was colocalized to the area stained with CMV late antigen. Sections from control specimens showed no immunoreactivity for CMV late antigen, COX-2 and MMP-9. These data seem to support the hypothesis that CMV may participate in a pathogenetic mechanism for atherogenesis or progression of atherosclerosis.

• 한국식품영양학회지
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• 제12권3호
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• pp.320-327
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• 1999

The flavonoids are one of the most numberous and widespread groups of natural consituents. The low molecular weight of benzo-${\gamma}$-pyrone derivative are ubiquitous in plants and are vegetables nuts, seeds, leaves, flowers, and bark. The flavonoids constitute of a large class of compounds ubiquitous in plants containing a number of phenolic hydroxyl groups attached to ring structures conferring the antioxidant activity. Epidemiologic studies suggest that the dietary intake of antioxidants constitutes a risk factor for vasclar disease indicating that oxidation may be important in the pathogenesis of human athero-sclerosis. Elevated plasma low density lipoprotein (LDL) cholesterol concentration are associated with accelerated atherosclerosis, LDL is oxidized by smooth muscle cells resulting in several chemicals and physical changes of LDL. Oxidized LDL is responsible for cholesterol loading of macrophages foam cells formation and atherogenesis. There have been insulficient tests of the protective effects of flavonoids against LDL oxidation to make definitive statements about their structure activity relationships. How-ever hydroxylation of the flavone uncleas can appears to be advantageous because polyhydroxylated aglycone flavonoids are potent inhibitor of LDL modification. This identification may lead to new and more effective antioxidant strategies for abrogating the atherosclerotic process the leading cause of death and disability in industrialized societies.

• 한국식품영양과학회지
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• 제15권3호
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• pp.306-312
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• 1986

Demonstration of the highly positive correlation between blood cholestrol levels and heart disease has made consumers wary of the fats in meat, milk and eggs. The egg, as perhaps the single largest common source of cholesterol, has been cited by many members of the medical and scientific world as a food contributing to heart disease. In light of decreasing per capita egg consumption and continuing dietary egg cholesterol controversy, many researchers have focused their efforts on egg nutrition. The results reported, however, are often contradictory. In spite of the disputable scientific evidence, the egg has been labelled (erroneously) as a highly cholesterogenic food. The objective of this presentation is to present a general picture of the problem and discuss our laboratory findings relevant to the problem. An isotope technique was utilized to incorporate $^{14}C$-cholesterol into egg yolk lipoproteins and study the metabolic fate of dietary ovo-cholesterol in rats. Two hundred and fifty micro-curies of 4-$^{14}C$-cholesterol, emulsified in corn oil, were orally administered to five Single Comb White Leghorn laying hens. Eggs were collected, hard-boiled, and the hot dried egg yolk powder (HEY) was prepared. Total radioactivity excreted via feces was determined. The rat groups fed egg yolk powder excreted more than 95% of the ingested ovo-cholesterol, whereas the rat chow group excreted only 47%. No difference was observed between HEY and CEY treatments. Therefore, an unknown lipid factor present in egg folk accelerates cholesterol turnover rate and excretion via feces.

• Biomolecules & Therapeutics
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• 제29권4호
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• pp.373-383
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• 2021

Atherosclerosis is the deposition of plaque in the main arteries. It is an inflammatory condition involving the accumulation of macrophages and various lipids (low-density lipoprotein [LDL] cholesterol, ceramide, S1P). Moreover, endothelial cells, macrophages, leukocytes, and smooth muscle cells are the major players in the atherogenic process. Sphingolipids are now emerging as important regulators in various pathophysiological processes, including the atherogenic process. Various sphingolipids exist, such as the ceramides, ceramide-1-phosphate, sphingosine, sphinganine, sphingosine-1-phosphate (S1P), sphingomyelin, and hundreds of glycosphingolipids. Among these, ceramides, glycosphingolipids, and S1P play important roles in the atherogenic processes. The atherosclerotic plaque consists of higher amounts of ceramide, glycosphingolipids, and sphingomyelin. The inhibition of the de novo ceramide biosynthesis reduces the development of atherosclerosis. S1P regulates atherogenesis via binding to the S1P receptor (S1PR). Among the five S1PRs (S1PR1-5), S1PR1 and S1PR3 mainly exert anti-atherosclerotic properties. This review mainly focuses on the effects of ceramide and S1P via the S1PR in the development of atherosclerosis. Moreover, it discusses the recent findings and potential therapeutic implications in atherosclerosis.

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.135-144
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• 2010

The pro-oxidative and pro-inflammatory pathways in vascular endothelium have been implicated in the initiation and progression of atherosclerosis. In fact, inflammatory responses in vascular endothelium are primarily regulated through oxidative stress-mediated signaling pathways leading to overexpression of pro-inflammatory mediators. Enhanced expression of cytokines, chemokines and adhesion molecules in endothelial cells and their close interactions facilitate recruiting and adhering blood leukocytes to vessel wall, and subsequently stimulate transendothelial migration, which are thought to be critical early pathologic events in atherogenesis. Although interleukin-4 (IL-4) was traditionally considered as an anti-inflammatory cytokine, recent in vitro and in vivo studies have provided robust evidence that IL-4 exerts pro-inflammatory effects on vascular endothelium and may play a critical role in the development of atherosclerosis. The cellular and molecular mechanisms responsible for IL-4-induced atherosclerosis, however, remain largely unknown. The present review focuses on the distinct sources of IL-4-mediated reactive oxygen species (ROS) generation as well as the pivotal role of ROS in IL-4-induced vascular inflammation. These studies will provide novel insights into a clear delineation of the oxidative mechanisms of IL-4-mediated stimulation of vascular inflammation and subsequent development of atherosclerosis. It will also contribute to novel therapeutic approaches for atherosclerosis specifically targeted against pro-oxidative and pro-inflammatory pathways in vascular endothelium.

• Journal of Nutrition and Health
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• 제44권6호
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• pp.465-473
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• 2011

Dietary fatty acids are under intense research to identify anti-atherogenic mechanisms, so we investigated green tea powder (GT) as a protector against atherogenesis originating from lipid peroxidation such as 4-hydroxynonemal (4-HNE) and malondialdehyde (MDA) in different dietary fatty acid-treated apo E KO mice. Growth rate and dietary efficiency were lower in apo E KO mice with or without LA compared to wild type. Plasma total cholesterol (TC) and triacylglycerol (TG) did not correspond to values in other tissues, but TG in heart tissue decreased significantly by GT after linoleic acid (LA) or docosahexaenoic acid (DHA) was administered. LA induced apoptosis as evidenced by changes in aorta morphology and immunohistochemistry. Lipid peroxides (LPO) was increased in apo E KO mice with or without LA corresponding to the accumulation of 4-HNE or MDA in the proximal aorta above the atria. GT consumption tended to reduce the primary causal mechanism of atherogenic phenomena such as oxidizability in both LA and DHA treated atherogenic mice. A high polyunsaturated fatty acids (PUFA) diet involved the changes on stress-induced apoptotic signaling by increasing caspase 3, cytochrome c, and nuclear factor-${\kappa}B$ in the heart tissue, but decreasing the bcl-2 protein. However, GT remarkably reduced the expression of apoptotic signaling, in contrast to the PUFA diet. Therefore, the potential of GT as an anti-atherosclerotic dietary antioxidant was tested in this study.

• 한국식품위생안전성학회지
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• 제16권4호
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• pp.342-348
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• 2001

본 연구는 동맥경화의 원인으로 알려진 사람 oxidized low density lipoprotein (LDL)에 대한 chitin sulfate의 산화억제 효과에 대하여 실험하였다. 사람 LDL을 쥐의 마크로파지 유도 oxidized LDL로 산화시킬 때 chitin sulfate를 첨가하여 TBARS와 전기영동에 의한 이동상 및 $O_2$소거 기능을 확인하였다. 사람 LDL에 macrophage를 이용해서 LDL을 산화시킬 때 chitin sulfate를 50~100 $\mu$M 첨가하였을 때 억제 효과가 높았으며, chitin sulfate를 100 $\mu$M 첨가하였을 때 LDL의 산화가 거의 억제되었고, 전기영동에 의한 이동거리도 100 $\mu$M chitin sulfate에서 완전히 억제되었다. 그리고 phorbol myristate acetate를 처리한 마크로파아지 유도 활성 산소의 소거 효과는 chitin sulfate의 농도가 100$\mu$M일 때 거의 소거하였다. 이상의 결과로 보아 chitin sulfate는 동맥경화의 예방에 효과적이라는 결론을 얻었다.

• 한국식품위생안전성학회지
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• 제26권3호
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• pp.254-259
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• 2011

본 연구에서는 동맥경화의 원인으로 알려진 사람 low density lipoprotein (LDL)에 대한 garlic oil의 산화억제 효과에 대하여 실험하였다. Garlic oil을 HPLC로 분석한 결과 diallyl disulfide, diallyltrisulfide, diallyltetrasulfide and diallyl pentasulfide 등의 유황화합물이 많이 들어 있었다. 사람 LDL을 $Cu^{2+}$ 및 macrophages 유도 oxidized LDL로 산화시킬 때 garlic oil을 20~60${\mu}g$/mL 범위에서 첨가하며 실험하였을 때 용량 의존형으로 억제되었고, garlic oil을 60 ${\mu}g$/mL 첨가하였을 때 LDL의 산화가 거의 억제되었으며, 산화 LDL의 전기영동에 의한 이동거리도 60 ${\mu}g$/mL 농도에서 거의 억제되었다. 그리고 garlic oil은 동맥의 내피세포에서도 용량 의존형으로 억제효과를 나타내었다. 또한 garlic oil은 tocopherol, ascorbic acid 보다 약간 높은 억제효과를 나타내었다. 이상의 결과에 따르면 garlic oil은 macrophage 및 내피세포에서 LDL의 항산화 효과가 있어 LDL의 산화 억제효과가 있는 것으로 나타났다.

• Toxicological Research
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• 제29권3호
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• pp.195-201
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• 2013

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

• BMB Reports
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• 제33권2호
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• pp.148-154
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• 2000

The glycation process plays an important role in accelerated atherosclerosis in diabetes, and the uptake of atherogenic lipoproteins by macrophage in the intima of the vessel wall leads to foam cell formation, an early sign of atherosclerosis. Besides the lipolytic action on the plasma triglyceride component, lipoprotein lipase (LPL) has been reported to enhance the cholesterol uptake by arterial wall cells. In this study, some properties of LPL-mediated low-density lipoprotein (LDL) uptake and the effect of LDL glycation were investigated in RAW 264.7 cell, a murine macrophage cell line. In the presence of LPL, $^{125}I$-LDL binding to RAW 264.7 cells was increased in a dose-dependent manner. At concentrations greater than $20\;{\mu}g/ml$ of LPL, LPL-mediated LDL binding was increased about 17-fold, achieving saturation. Without LPL, both very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) were ineffective in blocking the binding of $^{125}I$-LDL to Cells. However, LPL-enhanced LDL binding was inhibited about 50% by the presence of VLDL, while no significant effect was observed with HDL. Heat inactivation of LPL caused a 30% decrease of LDL binding. In the presence of LPL, the cells took up 40% of cell-bound native LDL. No significant difference was observed in cell binding between native and glycated LDL. However, the uptake of glycated LDL was significantly greater than that of native LDL, reaching to 70% of the total cell bound glycated LDL. These results indicate that LPL can cause the significant enhancement of LDL uptake by RAW 264.7 cells and the enhanced uptake of glycated LDL in the presence of LPL might play an important role in the accelerated atherogenesis in diabetic patients.