• Korean Journal of Community Nutrition
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• v.13 no.5
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• pp.713-722
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• 2008

The purpose of this study was to investigate the association among nutrient intakes and health-related lifestyles with cardiovascular disease risk assessed by blood lipid profile according to Apolipoprotein E genotypes. Middle-aged industrial male workers who had completed their annual medical examination were recruited and data of 675 subjects who finished the nutrient survey were used in the analysis. Anthropometric parameters, dietary assessment (FFQ), health-related lifestyles and blood profiles were used for statistical analyses. Apo E genotype groups were classified into the following three genotypes: Apo E2 group (including E2/E2, E2/E3, E2/E4), Apo E3 group (including E3/E3), Apo E4 group (including E3/E4, E4/E4). The frequency of Apo E2, E3, and E4 allele were 13.3%, 75.0% and 11.7% respectively. There were no significant differences in the anthropometric parameters depending on different Apo E genotypes. Also, no significant differences in the nutrient intakes were found according to the genotype groups. The nutrient intakes of all subjects were similar to or higher than the level of KDRIs (Dietary Reference Intakes For Koreans) except for intakes of calcium (67.44% of KDRIs), vitamin A (73.83% of KDRIs) and vitamin $B_2$ (78.02% of KDRIs). Also, there were no significant differences of health-related lifestyles according to Apo E genotype groups. As for the lipid profiles, Apo E4 group had significantly higher total and LDL-cholesterol concentrations than the Apo E2 group (p < 0.05). We confirmed that plasma total and LDL-cholesterol concentrations were greatly influenced by Apo E genotypes. However, nutrient intakes and health-related lifestyles were not associated with Apo E genotypes.

• Biomedical Science Letters
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• v.11 no.4
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• pp.429-434
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• 2005

Apolipoprotein E (apoE) restriction isotyping used oligonucleotides to amplify apoE gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on $4\%$ agarose gel. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and] 58cys (E2). DNA was isolated from 72 study participants and apoE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, $38 (52.8\%)$ had apo E4/4 or E3/4 (Group E4), $28(38.9\%)$ had the apo E3/3 genotype (Group E3) and $6(8.3\%)$ had apo E2/2 or E2/3 (Group E2). This genotypic information may help to identify individuals at increased risk for several diseases.

• Molecules and Cells
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• v.37 no.11
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• Journal of Nutrition and Health
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• v.33 no.6
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• pp.639-646
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• 2000

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.1
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• pp.225-232
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• 1999

Apo E polymorphism(e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal variation in plasma cholesterol concentrations. Among 62 normolipidemic healthy females, aged 19 up to 22 years, the relative frequencies of E3/3 was 0.806(n=50), E3/2 was 0.081(n=5), E3/4 allele was 0.113(n=7), and no E2/2, E2/4 and E4/4 were found. Based on the five samples of E2 allele, five subjects were randomly selected by E3 and E4 groups for the study of effects of apo E polymorphism on the distribution of serum lipid and amino acids profiles. No differences in the anthro pometric data among apo E isomers were found, otherwise the pulsation was higher in E4 than that in the others. There were no differences in plasma total HDL , HDL3 , HDL2 & LDL cholesterol, and apo A I concentrations. However, phenotype means significantly rank E2>E3>E4 allele in average TG levels(p=0.014), and rank E4>E3>E2 in total cholesterol levels(p=0.011). Atherogenic index(AI) such as lipoproteins was significantly increased in E2 & E4 than that in E3(p=0.045). Subjects with E3/2 allele had significantly higher concentrations of glutamine, phosphoserine and taurine, while subjects with E3/4 allele showed significantly lower concentrations of arginine and am inobutyrate and elevated level of phosphoserine in plasma com pared to those of E3/3 allele. Higher level of plasma taurine in subjects with E3/2 or E3/4 allele appears to be related to the elevated level of plasma total and LDL cholesterol concentrations compared to those of E3/3 allele.

• Nutrition Research and Practice
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• v.18 no.5
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• pp.617-632
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• 2024

BACKGROUND/OBJECTIVES: Atherosclerosis particularly due to high circulating level of low-density lipoprotein is a major cause of cardiovascular diseases. Ellagic acid is a natural polyphenolic compound rich in pomegranates and berries. Our previous study showed that ellagic acid improved functionality of reverse cholesterol transport in murine model of atherosclerosis. The aim of this study is to investigate whether ellagic acid inhibited inflammation-associated atherosclerotic plaque formation in cholesterol-fed apolipoprotein E (apoE)-knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE-KO mice were fed a cholesterol-rich Paigen diet for 10 weeks to induce severe atherosclerosis. Concurrently, 10 mg/kg ellagic acid was orally administered to the apoE-KO mice. Plaque lesion formation and lipid deposition were examined by staining with hematoxylin and eosin, Sudan IV and oil red O. RESULTS: The plasma leukocyte profile of cholesterol-fed mice was not altered by apoE deficiency. Oral administration of ellagic acid attenuated plaque lesion formation and lipid deposition in the aorta tree of apoE-KO mice. Ellagic acid substantially reduced plasma levels of soluble vascular cell adhesion molecule and interferon-γ in Paigen diet-fed apoE-KO mice. When 10 mg/kg ellagic acid was administered to cholesterol-fed apoE-KO mice, the levels of CD68 and MCP-1 were strongly reduced in aorta vessels. The protein expression level of nitric oxide synthase-2 (NOS2) in the aorta was highly enhanced by supplementation of ellagic acid to apoE-KO mice, but the expression level of heme oxygenase-1 (HO-1) in the aorta was reduced. Furthermore, ellagic acid diminished the increased aorta expression of the inflammatory adhesion molecules in cholesterol-fed apoE-KO mice. The treatment of ellagic acid inhibited the scavenger receptor-B1 expression in the aorta of apoE-KO mice, while the cholesterol efflux-related transporters were not significantly changed. CONCLUSION: These results suggest that ellagic acid may be an atheroprotective compound by attenuating apoE deficiency-induced vascular inflammation and reducing atherosclerotic plaque lesion formation.

• Journal of Microbiology and Biotechnology
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• v.17 no.6
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• pp.1024-1030
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• 2007

We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal model system for age-related macular degeneration (AMD). Transgenic mice expressing human apoE2 and C57BL/6J mice were fed normal chow or a high-fat diet for 4 weeks. Eyes were collected from the mice and lipid deposits in retinal pigment epithelium (RPE) were assessed using electron microscopy. The expressions of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular markers for angiogenesis, were assessed with immunohistochemistry. Eyes from apoE2 mice, regardless of diet, contained lipid accumulation in RPE under electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation was found predominantly in the RPE and the Bruch's membrane and increased in the eyes of apoE2 mice after one month of a high-fat diet ($8{\pm}2\;per\;50{\mu}m^2$ for normal chow and $11{\pm}2\;per\;50\;{\mu}m^2,\;p<0.05)$. ApoE expression was similar in the apoE2 and control mice; however, VEGF and bFGF were overexpressed in the retinal pigment epithelium of apoE2 eyes compared with control eyes, and PEDF expression was slightly decreased. These expression patterns of VEGF, bFGF, and PEDF suggest angiogenesis is progressing in apoE2 eyes. In conclusion, the eyes of apoE2 mice develop typical lipid accumulations, a common characteristic of AMD, making them a suitable animal model for AMD. The expression profile of VEGF and bFGF on the retinal pigment epithelium suggests that apoE2 may induce neovascularization by altering angiogenic cytokines.

• Nutrition Research and Practice
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• v.18 no.2
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• pp.194-209
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• 2024

BACKGROUND/OBJECTIVES: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.

• Journal of Sasang Constitution and Immune Medicine
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• v.15 no.1
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• pp.60-71
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• 2003

The purpose of this study was to investigate the effects of medical nutrition therapy(MNT) on plasma lipid levels of hyperlipidemic patients with apo E3 genotype according to Sasang Constitutions. From March to July, 2001, the 33 hyperlipidemic patients admitted to K University Medical Center were studied. The study subjects were classified according to their Sasang constitutions by QSCC II questionnaire which have been used at K University Oriental Medical Center. The anthropometric assessments, blood analysis, and apo E genetic typing were carried out. Nutrient intake was determined by food record method of food taken during two weekdays and one weekend. The MNT including the instruction for hypolipidemic and hypocholesterolemic diet (step l diet) was performed for 12 weeks. The results are as follow; (1) The mean age of hyperlipidemic patients was $49.91{\pm}8.48$ years. (2) The distributions of Sasang Constitution were 60.6% of Tae-eum, 21.2% of So-yang, and 18.2% of So-eum. The distributions of apo E genotype were 6.5% of apo E2/3, 78.8% of apo E 3/3, and 15.2% of apo E 3/4. (3) The nutrient consumption of the apo E3 subjects before the MNT showed lower calorie, iron, calcium, and vitamin B2 intakes than the RDAs for each nutrients with no significant differences among the constitutions. After 12-week of MNT, only the fat consumption was decreased in the Tae-eum group. The MNT did not change the pattern of food intake. (4) The plasma level of triglyceride, total cholesterol, and LDL-C were not changed after MNT in the three constitutional groups. The level of HDL-C was significantly increased significantly in Tae-eum and So-yang group and the level of homocystein was lowered in Tae-eum group after MNT. It could be concluded that the 12-weeks MNT with hypolipidemic and hypocholesterolemic diet did not change the level of total cholesterol, triglyceride, and LDL-C effectively regardless of Sasang constitutions even though the subjects' dietary intake was improved by MNT.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1099-1112
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• 2023

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.