• BMB Reports
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• v.51 no.10
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• pp.520-525
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• 2018

Cardiovascular diseases arising from atherosclerosis are the leading causes of mortality and morbidity worldwide. Lipid-lowering agents have been developed in order to treat hypercholesterolemia, a major risk factor for atherosclerosis. However, the prevalence of cardiovascular diseases is increasing, indicating a need to identify novel therapeutic targets and develop new treatment agents. Adenosine receptors (ARs) are emerging as therapeutic targets in asthma, rheumatoid arthritis, cancer, ischemia, and inflammatory diseases. This study assessed whether LJ-1888, a selective antagonist for $A_3$ AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out ($ApoE^{-/-}$) mice who are fed a western diet. Plaque formation was significantly lower in $ApoE^{-/-}$ mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of $ApoE^{-/-}$ mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in $ApoE^{-/-}$ mice administered LJ-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that LJ-1888, a selective antagonist for $A_3$ AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia.

• Journal of Lipid and Atherosclerosis
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• v.7 no.2
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• pp.122-154
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• 2018

Familial hypercholesterolemia (FH) is typically associated with single gene mutation that is inherited by autosomal dominant manner. Due to high cardiovascular risk, aggressive discovery, diagnosis, and treatment of FH are critical. Although FH is being increasingly spotlighted, we do not have sufficient data on Korean patients with FH. Here, we present the content of symposium of the Education Committee, Korean Society of Lipid and Atherosclerosis held in May 2018: 1) epidemiology, clinical diagnosis, Korean FH data, and regulation in Korea; 2) genes associated with FH, sequencing process in suspicious proband, cascade screening, and difficulty in genetic diagnosis in FH; 3) the importance of lipid-lowering therapy in FH, conventional and novel therapeutics for FH; 4) diagnosis of FH in children and adolescence, screening, and treatment of FH in children and adolescence; 5) history of FH studies in Korea, the structure and current status of FH registry of Korean Society of Lipid and Atherosclerosis; and 6) difficulty in diagnosis of heterozygous and homozygous FH, drug intolerance and achievement of treatment target. Discussion between speakers and panels were also added. We hope that this article is helpful for understanding FH and future studies performed in Korea.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.585-591
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• 2022

Background: Korean Red Ginseng (KRG) extract has been shown to have beneficial effects in patients with atherosclerosis, suggesting that KRG extract may be effective in preventing subsequent ischemic stroke in patients with severe atherosclerosis. Methods: This double-blind, placebo-controlled trial randomized patients with severe atherosclerosis in major intracranial arteries or extracranial carotid artery, to ginseng group and placebo group. They were given two 500-mg KRG tablets or identical placebo tablets twice daily for 12 months according to randomization. The primary endpoint was the composite of cerebral ischemic stroke and transient ischemic attack during 12 months after randomization. The secondary endpoints were change in volumetric blood flow of the intracranial vessels and the incidence of newly developed asymptomatic ischemic lesions. Any adverse events were monitored. Results: Fifty-eight patients were randomized from June 2016 to June 2017, 29 to ginseng and 29 to placebo, and 52 (28 and 24, respectively) completed the study. One patient in the placebo group, but none in the ginseng group, experienced ischemic symptoms (p = 0.46). Changes in volumetric blood flow and the presence of ischemic brain lesions did not differ significantly in the two groups, and none of these patients experienced adverse drug reactions. Conclusion: Ginseng was well tolerated by patients with severe atherosclerosis, with these patients showing good compliance with ginseng dosing. Ginseng did not show significant effects compared with placebo, although none of the ginseng-treated patients experienced ischemic events. Long-term studies in larger patient populations are required to test the effect of ginseng.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.467-476
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• 2010

Object : The purpose of this study was to investigate the correlation of atherosclerosis risk factors and pulse wave velocity (PWV) of carotid-femoral artery with Sasang constitution. This study also aimed to investigate the relationship between PWV and risk factors of atherosclerosis, including serum cholesterol and homosisteine, hs-CRP. Methods : We enrolled 160 patients without experience strokes who visited our hospital for a medical examination from January 1, 2008 to April 30, 2010 except patients whose body constitutions were undetermined according to QSCCII. We investigated the correlation between serum cholesterol values, blood pressure, body mass index(BMI), homosistein, hs-CRP and PWV. Pearson's correlation and partial correlation analysis were applied to examine the relationship between PWV and risk factors of atherosclerosis. Result : Among the 160 subjects, 54 were Taeumin, 54 were Soyangin, and 52 were Soeumin. The prevalences of high BMI (P-value <0.01), high hs-CRP(P-value <0.05), and high PWV(P-value <0.05) of Taeumin were higher than those of the other constitutions. PWV of carotid-femoral artery was significantly different among the three constitutional groups(Taeumin: $8.12{\pm}1.64m/sec$, Soyangin: $7.48{\pm}1.16m/sec$, Soeumin: $7.49{\pm}1.12m/sec$)(P-value <0.05). This research has show a statistical significance between the average amount of carotid-femoral artery PWV that is higher in Taeumin. Age factor of Taeumin was the effective determinant of the increase of mean PWV of carotid-femoral arteries. Conclusions : There were significant differences in the prevalence of atherosclerosis according to Sasang constitution. This study showed that atherosclerosis was more prevalent in Taeumin. Therefore, according to our results, risk of atherosclerosis was higher in Taeumin than among other constitutions.

• Journal of Food Hygiene and Safety
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• v.11 no.4
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• pp.243-259
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• 1996

This study was performed to investigate the induction of experimental atherosclerosis in rats and inhibitory effects of aloe vera on progression of atherosclerosis in rats. Adose range finding study of cholesterol and vitamin D2 for the induction of atherosclerosis and studies on the subchronic effect of aloe vera and on the chronic effect of aloe vera were carried out. A total of 3-week old 125 male rats of Sprague-Dawley were divided into 25 groups and fed with the diet containing cholesterol (0.1, 0.2, 0.3, 0.5, 1.0 and 2.0%) and vitamin D2 (500, 5000, 50000 and 500, 000 IU/100 g) for 4 weeks. 35 male rats were divided into 7 groups and fed with the diet containing aloe vera with 1.0% of cholesterol and 50, 000 IU/100 g of vitamin D2 for 4 weeks. 200 male rats were divided into 5 groups and fed with cholesterol and vitamin D2 for 6 and 12 months. Growth, clinical and pathological changes of rats in the three experiments were observed. The results were as follows: 1. In the dose-range finding study, feed intake, feed efficiency ratio and weight to body weight were increased in all of the feed groups containing 500, 000 IU/100 g of vitamin D2. Serum biochemical values of total cholesterol, high-density lipiprotein cholesterol (HDL-cholesterol), triglyceride, calcium, inorganic phosphorous and chloride of male rats in treated groups. The aorta and coronary artery of rats in all of the diet group containing 500, 000 IU/100 g of vitamin D2 showed typical atherosclerotic lesions. 2. Male rats fed with the diet containing aloe vera with 1.0% cholesterol and 50, 000 IU/100 g of vitamin D2 for 6 and 12 months did not show significant difference of diet intake and weight gain, and relative organ weight. The level of serum HDL-cholesterol and triglyceride recovered to the normal range by the aloe vera ingestation. 3. The aorta showed irregular appearence in the tunica intima with swelling, necrosis and calcification. The aorta of rat fed aloe vera diet showed no pathological lesions such as atherosclerosis of aorta. Aloe vera could have a helpful effect of vitamin D2 and cholesterol induced atherosclerosis in rats. Long-term supplementation of aloe vera may slow down the process of experimental atherosclerosis in rats have effects on the development of atherosclerosis.

• Proceedings of the KSME Conference
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• 2005.11a
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• pp.59.2-59.2
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• 2005

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.3
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• pp.399-407
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• 2012

To evaluate age and gender differences in the relation of cardiovascular risk factors, cognitive impairment, and subclinical carotid atherosclerosis from aged people using by a cross sectional method. Sixty-nine healthy elders living in the community who had not previously undergone carotid ultrasonography were included. We conducted life style surveys, and cognitive function tests including Korean-mini-mental state examination (K-MMSE) and clinical dementia rating-Korean. Various biomarkers from blood were assessed; fasting insulin-like growth factor-1, lipid-profile, high sensitivity C-reactive protein, total homocysteine, glucose, insulin, Homeostasis model assessment (HOMA) for insulin resistance index, vitamin B12, and folate level. Carotid intima-media thickness (C-IMT), and plaques were measured using carotid ultrasonography and aortic ultrasonography, a valid index of atherosclerosis. For the elderly subjects (aged 65-82 years), cognition impairment was more prevalent in females while subclinical atherosclerosis was more prevalentin males. Increased C-IMT has been kept in males, and C-IMT shows increasing trend and the peak at about 80 year-old in females with increasing age. The significant correlations between C-IMT and many vascular risk factors including age, triglyceride, abnormal homocysteinein male, and K-MMSE, insulin, HOMA index and abnormal aortic ultrasonography in female were different in each gender, with the exception of homocysteine (p<0.05). This data suggests that there were differences of age and gender characteristics in terms of subclinical atherosclerosis, cognitive impairment and vascular risk factors in community-living elders. Further larger and longitudinal studies across entire age are required to better understand the effects of risk factors on subclinical atherosclerosis.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.13.1-13.12
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• 2018

We aimed to explore whether changes in circulating levels of miRNAs according to type 2 diabetes mellitus (T2DM) or prediabetes status could be used as biomarkers to evaluate the risk of developing the disease. The study included 462 patients without T2DM at baseline from the CORDIOPREV trial. After a median follow-up of 60 months, 107 of the subjects developed T2DM, 30 developed prediabetes, 223 maintained prediabetes and 78 remained disease-free. Plasma levels of four miRNAs related to insulin signaling and beta-cell function were measured by RT-PCR. We analyzed the relationship between miRNAs levels and insulin signaling and release indexes at baseline and after the follow-up period. The risk of developing disease based on tertiles (T1-T2-T3) of baseline miRNAs levels was evaluated by COX analysis. Thus, we observed higher miR-150 and miR-30a-5p and lower miR-15a and miR-375 baseline levels in subjects with T2DM than in disease-free subjects. Patients with high miR-150 and miR-30a-5p baseline levels had lower disposition index (p = 0.047 and p = 0.007, respectively). The higher risk of disease was associated with high levels (T3) of miR-150 and miR-30a-5p ($HR_{T3-T1}=4.218$ and $HR_{T3-T1}=2.527$, respectively) and low levels (T1) of miR-15a and miR-375 ($HR_{T1-T3}=3.269$ and $HR_{T1-T3}=1.604$, respectively). In conclusion, our study showed that deregulated plasma levels of miR-150, miR-30a-5p, miR-15a, and miR-375 were observed years before the onset of T2DM and pre-DM and could be used to evaluate the risk of developing the disease, which may improve prediction and prevention among individuals at high risk for T2DM.

• Journal of Yeungnam Medical Science
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• v.27 no.2
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• pp.91-97
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• 2010

Endothelial cells play a key role in pathological processes such as cancer cell metastasis, atherosclerosis, and diabetic retinopathy. Vascular smooth muscle cells directly involve in the formation of atheroma in atherosclerosis. Some kinds of the endothelial cells are simply harvested from the umbilical veins, the tunica intima of aortic walls, the retina using various enzymes solutions. Those purely isolated cells provide a powerful tool in vitro studies of the endothelial cell related diseases. In this context, the cultured smooth muscle cells after the isolation from the tunica media of aortic walls are also used for elucidating the pathogenesis of atherosclerosis. Here, I briefly introduce articles that include the isolation of human umbilical vein endothelial cells(HUVEC), aortic endothelial and smooth muscle cells, retinal microvascular endothelial cells(RMEC), as well as the diseases' applications of these cells.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.2
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• pp.113-124
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• 2012

The oxidative modification of low density lipoprotein(LDL) has been implicated in the development of atherosclerosis. Oxidized LDL(oxLDL) is captured into macrophage and stimulates to form macrophage foam cell. And it can induce an inflammation and smooth muscle proliferation in atherosclerotic plaque. Objective : In this study, we aimed to investigate the effect of Bupleuri radix(SH) on the foam cell formation, a critical initiation stage of atherosclerosis. Methods : To achieve the goal, we examined the effect of SH on LDL oxidation, nitric oxide production in RAW264.7, and the effect of SH on cupuric sulfate-induced cytotoxicity, LDH release, and macrophage activity. Results : SH inhibited the formation of oxidized LDL from native LDL in RAW264.7 cell culture, and decreased the release of LDH from cupric sulfate-stimulated RAW264.7 cell. In other experiments, SH activated RAW264.7 cell, and prolonged the survival time, and inhibited foam cell formation induced by oxLDL in Raw 264.7 cells. Conclusion : These results showed that SH might prevent atherosclerosis by controlling the early stages of foam cell formation.