• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.265-270
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• 2004

Coronary heart disease (CHD) has been the number one killer in western society for a long time, and CHD in most instances is due to atherosclerosis. One of the earliest events in atherogenesis is the intracellular accumulation of lipids, particularly cholesterol esters, in the aortic intima. The lipids presumably came from the uptake of plasma lipoproteins, particularly from LDL. These foam cells were identified as being predominantly as macrophages. Currently, it is believed that oxidation of low density lipoprotein (LDL) might contribute to the generation of foam cells. An outcome of the oxidation hypothesis is that the consumption of antioxidants would be beneficial. In this study, Boldine, an alkaloid of Peumus boldus was tested for their antioxidant potency both in, in vitro oxidation system and in mouse models. Boldine decreased the ex-vivo oxidation of Low-density lipoprotein (LDL). In vivo studies were performed to study the effect of these compounds on the atherosclerotic lesion formation in LDL r-/- mice. Three groups of LDL r-/- mice (N=12 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 and 3 were given 1 and 5 mg of Boldine/day in addition to the atherogenic diet. The results indicated that there was a decrease in lesion formation reaching a 40% reduction due to Boldine compared to controls. The in vivo tolerance of Boldine in humans (has been used as an herbal medicine in other diseases) should make it an attractive alternative to vitamin E.

• Korean Circulation Journal
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• v.48 no.12
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• pp.1097-1119
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• 2018

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.269.2-270
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• 2002

Atherosclerosis is a main cause of cardiovascular diseases (that is angina. hypertension. cardiac infarction) and stroke. High level of low-density lipoproteins (LDL) in blood has been implicated as an important factor of atherosclerosis progression. Recently researches in endothelial cells unveiled the roles of Iysophosphatidylcholine (LPC). a constituent of oxidized LDL in atherosclerosis. (omitted)

• Reproductive and Developmental Biology
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• v.36 no.3
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• pp.147-154
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• 2012

This study was designed to determine whether low-density lipoproteins (LDL) from egg yolk and taurine, hypotaurine and trehalose as antioxidant in extender improve the freezability and fertility of Korean Jeju Black Bull semen. The semen was cryopreserved with tris egg yolk extenders containing 7% glycerol and treated 4% LDL, 20 mM taurine, hypotaurine and trehalose. Frozen-thawed sperm were evaluated motility, viability, membrane, and acrosome integrity and sperm penetration ability. The results were compared to semen cryopreserved in tris egg yolk extender only as control. Frozen-thawed semen evaluation cleary indicated that the addition of LDL and LDL-antioxidants (taurine, hypotaurine and trehalose) combination were significantly improved (p<0.05) the viability (%; with staining test using eosin-Y) compared to control spermatozoa. Also, in membrane integrity (%; with supravital hypo-osmotic swelling test), not only LDL-antioxiants combination but also LDL were significantly increased (p<0.05) the swelled sperm using HOST compared to control. Sperm acrosome integrity state was classified by CTC (chlortetracycline) staining test. F pattern was significantly increased in LDL-antioxidant combination than control (p<0.05) and B pattern was not significantly differences among all treatments and control. However, AR pattern was significantly decreased in LDL-antioxidants combination than control (p<0.05). Pronucleus formation and sperm penetration index (SFI) were significantly increased in LDL and LDL-antioxidants combination than control (p<0.05). Especially, LDL-taurine significantly improved pronucleus fomation and SFI than LDL (p<0.05). It was concluded that LDL and LDL-antioxidants in extender improved the freezability and fertility of Korean Jeju Black bull spermatozoa.

• BMB Reports
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• v.33 no.2
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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.

• Journal of Nutrition and Health
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• v.31 no.8
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• pp.1235-1243
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• 1998

Although an elevated plasma level of high density lipoprotein (HDL) is known as a protective component against the development of atherosclerosis and ensuing coronary heart diseases, the related mechanisms are still not established . It has been clearly demonstrated in the early stages of atherogenesis that adhesion of monocytes and lymphocytes to the vascular endothelium is enhanced via adhesion molecules, and that monocytes and macrophages accumulate in the subendothelial space. The present study has investigated whether isolated plasma HDL plays a role in protection against atherogenesis by inhibiting the expression of vascular cell adhesioin molecule-1(VCAM-1) on the endothelial cells. Effects of plasma native low density lipoprotein (LDL) and ac ethylated LDL(AcLDL) on VCAM-1 expression were also examined by using an immunocytochemical technique. While plasma HDL did not alter the basal expression of VCAM-1 , lipopolysaccharide(LPS) induction of this adhesion modlecule was markedly inhibited at a phyaiological concentration of HDL. In contrast, 30$\mu\textrm{g}$ protein/ml AcLDL increased sifnificantly both basal VCAM-1 expression and its LPD induction , suggesting that this modified LDL enhances leukocyte adhesiion to endothelial cells. Unlike AcLDL , plasma native LDL inhibited significantly VCAM-1 expression. This indicates that LDL did not undergo oxidative modificantion while incubated with endothelial cells. These results suggest that plasam HDL may inhibit atherogenesis by reducing the expression of adhesion molecules, which is a protective mechanism independent of tis reverse cholesterol transport function . Modified LDL is a potent iducer for adhesion molecules in vascular endothelical cells and could play a role in the pathogenesis of atherosclerosis by adhering to blood cells.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.4
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• pp.486-494
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• 2006

In order to protect the spermatozoa against cold shock, hen egg yolk is widely used as a cryoprotective agent in semen freezing extenders for domestic animals. The protective action of yolk is largely presumed to be due to low density lipoproteins (LDL). The effects of LDL on sperm quality of bull and northern pike (Esox lucius) after freezing-thawing have been reported, but no study has been made to evaluate the effect of LDL on boar sperm motility and other characteristics. The experiment was carried out to investigate the effect of LDL on the freezing of boar sperm in 0.25 ml straws. The aim was to evaluate the quality of boar spermatozoa cryopreserved in the presence of LDL. Motility of semen cryopreserved in LDL was analyzed and compared to semen cryopreserved with Tris-citric acid-glucose (TCG) and Tris-citric acid-fructose (TCF), two basic freezing extenders containing egg yolk. Similarly, acrosome and plasma membrane integrity were also evaluated and compared to semen cryopreserved with TCG and TCF. Analysis of sperm quality after freeze-thaw showed that the motility, acrosome and plasma membrane integrity were improved with LDL in the extender, as compared to the TCG and TCF. The highest post-thaw integrity of acrosome and plasma membrane and motility were obtained with 9% LDL (w/v). Consequently, the optimum LDL concentration in the extender was 9%. It is also suggested that the concentration of LDL addition is important for the effect on boar sperm protection during freezing and thawing. The percentage of motile spermatozoa was significantly higher after freezing in 9% LDL than in TCG and TCF 54.4% versus 30.4% and 30.1% (p<0.05), respectively. The integrity of acrosome and plasma membrane were also significantly higher at 70.3% and 50.5% respectively with semen frozen in 9% LDL extender compared to TCG at 37.8% and 30.3% and TCF at 36.4% and 29.9%, respectively (p<0.05),. In conclusion, we propose that extender containing LDL extracted from hen egg yolk could be used as a cryoprotective media with a better efficiency than TCG and TCF. LDL improved boar semen quality, allowing better spermatozoa motility, acrosome and plasma membrane integrity after the freeze-thaw process. Furthermore, we found out that the extender with 9% LDL concentration significantly enhanced motility, acrosome and plasma membrane integrity of boar sperm after freezing and thawing.

• Molecules and Cells
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• v.38 no.12
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• pp.1096-1104
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• 2015

Particulate $matter_{2.5}$ ($PM_{2.5}$) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which $PM_{2.5}$ aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous $PM_{2.5}$ solution on lipoprotein metabolism. Collected $PM_{2.5}$ from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. $PM_{2.5}$ extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. $PM_{2.5}$ treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by $PM_{2.5}$ solution in a dose-dependent manner. Further, $PM_{2.5}$ solution caused cellular senescence in human dermal fibroblast cells. Microinjection of $PM_{2.5}$ solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of $PM_{2.5}$ induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins.

• Preventive Nutrition and Food Science
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• v.1 no.1
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• pp.87-92
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• 1996

This study describes a stable and simple method for the measurement of cholesteryl ester transfer protein(CETP) activities using reconstituted HDL and LDL as substrates. Apolipoproteins (apo) A-I and -B were purified from hog plasma by a new strategy without ultracentrifugation and delipidation. a simple two-step column chromatography was administered. In the first step of phenyl-sepharose CL-4B column chro-matography, hydrophobic plasma proteins were isolated. The most hydrophobic proteins bound to the column appeared to be A-I and apo-B. Contaminat proteins were efficiently eliminated from the sample by washing the column with 0.3M NaCI containing buffer after loading the plasma on the column. Two pure proteins showing each single band on SDS-PSGE of apo A-I and apo-B were individually obtained by a subsequent gel filtration column chromatography(Sephadex G-200). This two-step purification was simple and inexpensive compared to the ultracentrifugation and/or delipidation method that are most commonly used. Reconstituted hight-density lipoproteins(HDL) and low-density lipoproteins(LDL) were prepared using the purified apo A-I and-B, respectively. When these artificially prepared HDL and LDL were used in the assays for CETP as the cholesteryl ester(CE) donor and acceptor respectively, the specific transfer of CE increased up to two fold compared to that used the native HSL and LDL.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.162-168
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• 2007

It is well known that oxidized low-density lipoprotein (oxLDL) is the most characterized humoral factor that plays an important role in the pathogenesis of atherosclerosis. The water extract of the Korean herbal remedy, ZoaGumHwan (ZGH), which is composed of roots of Coptis chinensis Franch and fruits of Evodia officinalis Dode with the ratio of 6 to 1, reduced the in vitro oxidation of low density lipoproteins (LDL). Also, the ZGH extract and berberine, one of the major components of ZGH, significantly prevented oxLDL-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVEC). Furthermore, the ZGH water extract and berberine decreased oxLDL-induced expression of CC chemokine receptor 2 (CCR2), a dominant monocyte chemotaxis receptor, in U937 human monocytic cells. The protective effects of the ZGH water extract and berberine were similar to those of simvastatin, an effective lipid-lowering drug. The results suggest that Korean herbal remedy, ZGH, seems to have protective effect against oxLDL-induced monocyte chemoattractant protein (MCP)-1/CCR2-dependent monocyte recruitment onto endothelial cells.