Dyslipidemia, defined as elevated triglyceride (TG), total- and LDL-C, and/or decreased HDL-C levels, is considered a principal risk factor for cardiovascular disease. The low-density lipoprotein receptor (LDLR) family has been considered a key player in the prevention of dyslipidemia. The LDLR family consists of cytoplasmic membrane proteins and plays an important role not only in ligand–receptor binding and uptake, but also in various cell signaling pathways. Emerging reports state that various functional ingredients dynamically modulate the function of the LDLR family. For instance, oats stimulated the LDLR function in vivo, resulting in decreased body weight and improved serum lipid profiles. The stimulation of LRP6 by functional ingredients in vitro activated the Wnt/β-catenin pathway, subsequently suppressing the intracellular TG via inhibition of SREBP1, PPARγ, and C/EBPα. Furthermore, the extract of Cistanchetubulosa enhanced the expression of the mRNA of VLDLR, followed by a reduction in the serum cholesterol level. In addition, fermented soy milk diminished TG and total cholesterol levels while increasing HDL-C levels via activation of LRP1. To summarize, modulating the function of the LDLR family by diverse functional ingredients may be a potent therapeutic remedy for the treatment of dyslipidemia and cardiovascular diseases.

This study was designed to determine whether low-density lipoporoteins (LDL) extracted from egg yolk in extender improve the function of Korean Jeju Black Bull semen. The semen was cryopreserved with 5% ethylene glycol (EG) or 7% glycerol (G) extenders containing 10% egg yolk (EY), 4% LDL and 5% EY or 8% LDL. Frozen-thawed sperm were evaluated sperm motility, viability, membrane integrity and acrosome integrity. Post-thawed sperm motility has been significantly higher (p<0.05) in 4% LDL + 5% EY (; EG and ; 7% G) than 8% LDL (; EG and ;G). Treatment of 4% LDL + 5% EY-EG () has been significantly improved sperm viability compared to other treatments except 10% EY - EG. Moreover, in membrane integrity, swollen sperm ratio has been only significantly increased (p<0.05) in 4% LDL + 5% EY - EG () among all treatments. In assess to detect acrosome integrity, especially, AR pattern ratio has been significantly decreased (p<0.05) in 4% LDL + 5% EY - EG among all treatments. In sperm viability as time passes, between 4% LDL + 5% EY and 10% EY, there was no significant difference, but 8% LDL was significantly decreased sperm viability in EG (1 and 2 hrs) and G (30 min, 1, 2, 5 and 12 hrs) extender. However, there were no significant differences among all treatments except 8% LDL-G in sperm membrane integrity. 8% LDL-G has been significantly decreased swollen sperm ratio at 5 hrs after thawed. It is concluded from these results that 4% LDL + 5% EY to the freezing extender showed more positive effect on the frozen-thawed spermatozoa in Korean Jeju Black bull.

Growing evidence indicates that oxidized low density lipoprotein (LDL) may promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. The inhibitory effected on the susceptibility of human LDL to Cu²+ or macrophages induced oxidation was investigated by monitoring thiobarbituric acid reactive substances (TBARS). Organosulfur compounds of garlic oil contains diallyldisulfide, diallyltrisulfide, diallyltetrasulfide, and diallyl pentasulfide in order. Garlic oil inhibited LDL oxidation by Cu²+, or macrophages in a dose dependently, with a 20~60 μg, as increased TBARS assay. Garlic oil, at 60 μM, almost completely inhibited macrophages induced increase in electrophoretic mobility of LDL. When compared with several other antioxidants, probucol showed highest ability,and then garlic oil showed a much higher ability than natural occurring antioxidants, α-tocopherol and ascorbic acid. The results suggested that garlic oil might play the inhibitory effects in the process of LDL oxidation.

저밀도 리포단백질 수용체 관련 단백질 5(LRP5)는 간과 췌장을 포함하여 많은 조직에서 발현하며 아포리포단백질 E와 결합한다. 이와 같은 LRP5 유전자의 체내 기능을 규명하기 위하여 LRP5 유전자가 결손된 생쥐를 개발하였다. 먼지 LRP5 genomic DNA는 TT2 ES 세포로부터 분리하였으며 LRP5 유전자의 엑손 18에 neo 유전자를 삽입한 vector를 구축하고 TT2 ES 세포에 도입하였다. 178개의 G418 내성을 보인 세포 중 상동유전자 재조합에 의하여 targeting vector가 LRP5 유전자 위치에 삽입된 clone은 3개였다. 키메라 생쥐는 상실배기 수정을 ES 세포와 응집시켜 생산하였으며 생산된 키메라 생쥐는 C57BL/6 생쥐와 교미를 유도하여 heterozygous를 얻었다. 또한 이들 heterozygous간의 교배에 의하여 LRP5 유전자 결손 생쥐를 생산하였다. 이러한 생쥐는 LRP5 유전자의 체내 기능연구에 있어서 모델로 이용될 것으로 생각된다.

Growing evidence indicates that oxidized low density Iipoprotein (LDL) may promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. The effect of chitin sulfate on the susceptibility of human low density lipoprotein (LDL) to macrophages-induced oxidation was investigated by monitoring a thiobarbituric acid reactive substance (TBARS). Chitin sulfate inhibited LDL oxidation by macro phages in a dose dependent manner, with a 50-100μM, as assessed by TBARS assay. Chitin sulfate, at 100 μM, almost completely inhibited the macrophage-induced increase in electrophoretic mobility of LDL. Also, chitin sulfate almost completely inhibit O₂^- at concentration of 100 μM. These observations suggest that chitin sulfate might be an effective in prevention of atherosclerosis.

The flavonoids are one of the most numberous and widespread groups of natural constituents. The low molecular weight of benzo-γ-pyrone derivatives 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 vascular disease, indicating that oxidation may be important in the pathogenesis of human atherosclerosis. 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. However, hydroxylation of the flavone nucleas 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.

This study was undertaken to evaluate antioxidative activities of substances isolated from marine resources against human low density lipoprotein (LDL). Methanol-water extract (80:20, v/v) of Sargassum ringgoldianum had the highest antioxidant activity and the active substance was purified by silica gel column chromatography by eluting chlorform : methanol mixture (80:20, v/v). The active fraction was separated to several spots on the TLC in chloroform : methanol (10:1, v/v) mixture. Antioxidative activity of band 4 of fraction 2 on TLC was highest than that of a-tocopherol against human LDL oxidation by the method of thiobarbituric acid reactive substance (TBARS). The band 4 of fraction 2 inhibited the copper mediated oxidation of human LDL with almost completely at 1 or 2 mg/ml.

해양 미생물로부터 사람 Low Density Lipoprotein(LDL)에 대한 항산화 활성 균주를 검색 하였든 바 부산 인근연안에서 항산화 활성이 높은 Bacillus sp. RH-5를 분리 동정하였다. Bacillus sp. RH-5의 항산화 활성물질의 생산 거 배지는 1.0% glucose, 0.25% polypeptone, 0.25% yeast extract, 0.01% FeSO_4?7H_2O, 50% sea water이였다. 이때 최적 조건은 pH 7.0, 배양 온도는 30℃ 및 배양 시간은 48시간에서 항산화 활성이 가장 높았다. 사람 LDL을 1~5 μM CuSO_4 존재하에서 산화 시킨 결과 Bacillus sp. RH-5 배양액의 ethyl acetate 추출물의 500 및 1,000 ㎍/ml에서 산화가 억제되었으며 또 5 μM CuSO_4 존재하에서 산화시킨 LDL의 전기영동거리는 native LDL보다 다소 높았으나 LDL에 ethyl acetate추출물을 첨가한 경우 그 이동거리는 native LDL과 거의 비슷하였다.

This study was pcrformed to evaluate the antioxidant activity of silymarin against human low density lipoproteins(LDL) oxidation. Silymarin extracted from Silybum marianum was successively purified with solvent fractionation and followed by silica gel column chromatography. The active substances were separated by HPLC and the isolated active substances, silymarin were identified by IR, NMR, GC-MS as silymarin. Silymarin inhibited at the 5 uM Cu^(2+)-mediated oxidation of human low density lipoprotein (LDL) in a dose dependent manner. Silymarin completely inhibited LDL oxidation at 50 ug/ml concentration. These findings suggest that silymarin may protect LDL against oxidation in atherosclerotic lessions.

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 Cu2+-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 Cu2+-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 (0~100 μg/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.