• Journal of Life Science
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• v.32 no.3
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• pp.256-262
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• 2022

Oxysterols are oxygenated metabolites of cholesterol generated by serial enzymatic reactions during bile acid synthesis. Similar to cholesterol, oxysterols move rapidly to the intracellular region and modulate various cellular processes, such as immune cell responses, lipid metabolism, and cholesterol homeostasis. Different nuclear transcription factors, such as glucocorticoid, estrogen, and liver X receptors, can be modulated by oxysterols in multiple tissues. The most abundant oxysterol, 27-hydroxycholesterol (27-OHC), is a well-known selective modulator that can either activate or suppress estrogen receptor activity in a tissue-specific manner. The contribution of 27-OHC in atherosclerosis development is apparent because a large amount of it is found in atherosclerotic plaques, accelerating the transformation of macrophages into foam cells that uptake extracellular modified lipids. According to previous studies, however, there are opposing opinions about how 27-OHC affects lipid and cholesterol metabolism in metabolic organs, including the liver and adipose tissue. In particular, the effects of 27-OHC on lipid metabolism are entirely different between in vitro and in vivo conditions, suggesting that understanding the physiology of this oxysterol requires a sophisticated approach. This review summarizes the potential effects of 27-OHC in atherosclerosis and metabolic syndromes with a special discussion of its role in metabolic tissues.

• Journal of health informatics and statistics
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• v.41 no.1
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• pp.49-56
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• 2016

Objectives: Carotid intima-media thickness (CIMT) and the presence of carotid artery plaque are widely used as preclinical markers of atherosclerosis. Due to operator dependency in measuring CIMT, it is important to evaluate the reliability of measuring CIMT and plaque between centers in a multicenter study. The purpose of this study is to evaluate the inter-rater reliability of CIMT and plaque presence among three clinical centers of the Cardiovascular and Metabolic Disease Etiology Research Center (CMERC). Methods: Twenty people without known cardiovascular disease (age 37-64) were enrolled during 2014-2015, and their left and right carotid arteries were examined repeatedly with ultrasonography for CIMT measurements at three clinical centers according to a predetermined protocol. Maximum and mean values of CIMT at distal common carotid artery were recorded. Plaque presence at a carotid artery was checked by an operator. The reliability of CIMT and carotid plaque presence was assessed using an intraclass correlation coefficient (ICC) and kappa statistics, respectively. Results: Calculated ICC was 0.647 (95% CI: 0.487-0.779) for maximum CIMT, and 0.758 (95% CI: 0.632- 0.854) for mean CIMT. In Bland Altman plot, most observed values were distributed within mean difference ${\pm}1.96$ SD ranges. Kappa statistics of plaque presence between two centers were 0.304 (center 1 and 2), 0.507 (center 1 and 3), and 0.606 (center 2 and 3), respectively, while Fleiss kappa for overall agreement was 0.445. Conclusions: The inter-rater reliability of CIMT measurements among three clinical centers turned out to be high, and the agreement of measuring carotid plaque presence was fair.

• Journal of Chest Surgery
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• v.42 no.4
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• pp.480-486
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• 2009

Background: The Fogarty thromboembolectomy catheter technique was devised to extract distal arterial emboli and it represents a milestone for the treatment of patients with acute arterial occlusion since the 1960s. The major causes of arterial occlusion have changed from emboli of a heart origin to atherosclerosis over the past 30 years. Accordingly, questions have been raised about the effectiveness of simple Fogarty thromboembolectomy. Material and Method: During the period from March 1990 through August 2008, 156 patients who requiring Fogarty thromboembolectomy were analyzed. The patients were divided into two groups: those with simple Fogarty thromboembolectomy (Group 1, 79 patients) and those with additional vascular bypass graft surgery (Group 2, 77 patients). The duration of symptoms, the cause of thrombi, admission via the emergency room, a history of acupuncture or misdiagnosis, combined diseases, the anatomic occlusion site and the cause of death were analyzed using T-tests, cross tab tests, Chi square tests and Kaplan-Meier tests, respectively. Result: The mean age was 64$\pm$10 years in the 2 groups. The duration of symptoms (pain) in Group 1 vs Group 2 was 12$\pm$4 days vs 71$\pm$14 days (p=0.001). 50 (63%) patients in Group 1 were admitted via the emergency room vs 18 (23%) patients in Group 2 (p=0.005). Misdiagnosis and the treatment for herniated intervertebral disc or acupuncture were given to, 20 (25%) patients in Group 1 vs 30 (39%) patients in Group 2. Anticoagulation treatment before admission was performed in 22 (28%) patients in Group 1 vs 11 (14%) patients in Group 2. The causes of thrombi were heart disease in, 24 (30%) patients in Group 1 vs 6 (8%) patients in Group 2 (p=0.001), atherosclerosis in 46 (58%) patients in Group 1 vs 67 (87%) patients in Group 2 (p=0.001) and trauma in 9 (11%) patients in Group 1 vs 6 (8%) patients in Group 2. The combined diseases were cerebrovascular accident, hypertension and diabetes mellitus in 22 $\sim$ 37% of the total patients. The occlusion sites were mainly in the iliac and femoral arteries. Endarterectomy was performed in 7 (9%) patients in Group 1 vs 18 (23%) patients in Group 2 (p=0.012). Treatment was successful in 27 (34%) patients in Group 1 and in 40 (52%) patients in Group 2 (p=0.019). Reocclusion occurred in 37(47%) patients in Group 1 vs 20 (26%) patients in Group 2 (p=0.000), Amputation was done in 4 (5%) patients in Group 1 vs 12 (16%) patients in Group 2 (p=0.012) and death occurred in 10 (13%) patients (Group 1) vs 3(4%) patients (Group 2) (p=0.044). Conclusion: The recent past has shown a decline in the effectiveness of simple Fogarty thromboembolectomy with a changing pattern of acute arterial occlusion from a rheumatic heart origin to atherosclerosis. Additional bypass procedures play a role for the treatment of arterial occlusion instead of always performing simple Fogarty thromboembolectomy.

• The Journal of Korean Medicine
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• v.22 no.3
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• pp.105-118
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• 2001

Objectives : The prescription of Semyung-Gangji-tang, designed for the treatment of hyperlipidemia and atherosclerosis, consists of herbs good for treating blood stasis and phlegm stagnancy. It invigorates the liver, kidneys and spleen. Its medical nature is not too cold or too hot and increases human vital energy. The purpose of this study is to examine the curative effects of Semyung-Gangji-tang on atherosclerosis in hyperlipidemic rabbits. Methods : Twenty-four male NZW rabbits, around 2kg of body weight, were divided into 4 groups. Group I served as the normal group. Group II served as the atherogenic model group, fed a 1 % cholesterol diet for 8 weeks and sacrificed. Group III served as the atherogenic control group, fed with a 1 % cholesterol diet for 8 weeks and with a normal diet for the next 4 weeks. Group IV served as the treatment group treated the same as the control group and medicated with Semyung-Gangji-tang for the last 4 weeks. Three animals of group I and six animals of group n were sacrificed at 8 weeks. Five animals of group I , five animals of group III and IV were sacrificed at 12 weeks. Pathological examinations and image analysis were performed on the collected tissue samples. Results : The percentage of lipid deposition area of thoracic aortas of group IV($41.74{\pm}8.93%$) at 12 weeks was decreased compared with the group III ($71.30{\pm}12.74%$) at 12 weeks, but a statistical difference was not observed. The percentage of group IV at 12 weeks was significantly decreased (P<0.05) compared with the group n ($76.41{\pm}7.43%$) at 8 weeks. Histopathologically, advanced atheromas with calcification of aortic arches were observed in all animals of the control group at 12 weeks, but were observed in 2 animals of the treatment group at 12 weeks. Histopathologically, atheromas with calcification of thoracic aortas were observed with major atherogenic lesions in control group at 12 weeks, but simple fibro-fatty streaks were observed major atherogenic lesions in treatment group at 12 weeks. Conclusions : These results indicate that Semyung-Gangji-tang has antiatherogenic effects on experimentally induced atherosclerosis in rabbits.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.407-419
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• 2002

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method： We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result： Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group： 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion： The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

• Progress in Medical Physics
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• v.16 no.4
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• pp.207-213
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• 2005

The severity of carotid Intima-media thickness (IMT) is an Independent predictor of atherosclerosis which causes transient cerebral ischemia, stroke, and coronary events such as myocardial Infarction. The IMT consists of Intima thickness (IT) and media thickness (MT). However, the Individual clinical significance of IT and MT has not been well studied. We devised a method of measuring IT, MT, and IMT using B-mode ultrasound Image processing technique for the diagnosis of atherosclerosis. To inspect the clinical significance of IT, MT, and IMT, one hundred forty-four consecutive patients (mean age; 57 years old, 72 males) were underwent common carotid artery scanning using high-resolution ultrasound. Results showed that, the IT (p<0.05), MT (p<0.05) as well as IMT (p<0.01) of patients with atherosclerotic disease were significantly thicker than that of the patients without atherosclerotic disease. Patients with hyperiension showed significantly thicker IT (p<0.01), MT (p<0.001), and IMT (p<0.001). However, only IT was thicker in patients with smoking (p<0.01). The IT (r=0.374, p=0.001), MT (r=0.433, p=0.000), and IMT (r=0.479, p=0.000) showed positive correlation with age. The coefficients of determination ($r^2$) were estimated to be $92.4\%$ for IMT and MT, $49.1\%$ for IMT and IT, and $27.4\%$ for IT and MT. This result suggests that the Intima layer of the carotid artery has a different physiology with the media layer.

• Journal of Chest Surgery
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• v.41 no.6
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• pp.687-694
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• 2008

Background: Although aortic valve sclerosis causes no significant hemodynamic alterations, it is associated with an increased risk of cardiovascular death and myocardial infarction. However, the role of ${\beta}_3$ integrin in aortic valve sclerosis remains unclear. Material and Method: Twenty male New Zealand rabbits were divided into two groups. Group 1 rabbits (n=10) received a normal chow diet, while group 2 (n=10) rabbits received a diet containing 1% cholesterol for 12 weeks. After the rabbits were euthanized, their aortic valves and ascending aortas were excised for analysis. Result: Total serum cholesterol ($2,148.3{\pm}1,012.5\;mg/dL$ versus $53.7{\pm}31.8\;mg/dL$, p<0.05), triglyceride ($240.4{\pm}218.3\;mg/dL$ versus $31.6{\pm}6.4\;mg/dL$, p<0.05), and low density lipoprotein (LDL)-cholesterol($2,065.3{\pm}960.9\;mg/dL$ versus $29.1{\pm}30.9\;mg/dL$, p<0.05) levels were significantly higher in the cholesterol diet group compared with the normal diet group. Myofibroblasts and macrophages were more highly expressed in the aortic valve leaflets of rabbits in the cholesterol diet group than of those in the normal diet group. A real-time polymerase chain reaction revealed decreased ${\beta}_3$ integrin mRNA levels in the hypercholesterolemic aortic valves and aortas. Conclusion: The present study shows that hypercholesterolemia induces aortic valve sclerosis. These findings suggest that alterations in ${\beta}_3$ integrin may playa role in the development of aortic valve sclerosis.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.245-252
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• 2020

Macrophage cell death contributes to the formation of plaque, leading to the development of atherosclerosis. The accumulation of triglyceride (TG) is also associated with the pathogenesis of atherosclerosis. A previous study reported that TG induces the cell death of macrophages. This study examined whether the cytoplasmic release of cathepsin B from lysosome is associated with the TG-induced cell death of macrophage. The release of cathepsin B was increased in the TG-treated THP-1 macrophages, but the TG treatment did not affect cathepsin B expression. Furthermore, the inhibition of cathepsin B by its inhibitor, CA-074 Me, partially inhibited the TG-induced cell death of macrophage. TG-triggered macrophage cell death is mediated by the activation of caspase-1, -2, and apoptotic caspases. Therefore, this study investigated whether cathepsin B is implicated in the activation of these caspases. The inhibition of cathepsin B blocked the activation of caspase-7, -8, and -1 but did not affect the activity of caspase-3, -9, and -2. Overall, these results suggest that TG-induced cytoplasmic cathepsin B causes THP-1 macrophage cell death by activating caspase-1, leading to subsequent activation of the extrinsic apoptotic pathway.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.1
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• pp.8-16
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• 2008

Purpose: To assess the effect of extracranial-intracranial (EC-IC) bypass surgery on hemodynamic improvement, we evaluated serial regional cerebral hemodynamic change of the middle cerebral artery (MCA) in symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or MCA using $^{99m}Tc$-ECD acetazolamide stress brain perfusion SPECT (Acetazolamide SPECT). Materials and Methods: The patients who had suffered a recent stroke with atherosclerotic ICA or MCA occlusion underwent EC-IC bypass surgery and Acetazolamide SPECT at 1 week before and three to six months after surgery. For image analysis, attenuation corrected images were spatially normalized to SPECT templates with SPM2. Anatomical automated labeling was applied to calculate mean counts of each Volume-Of-Interest (VOI). Seven VOIs of bilateral frontal, parietal, temporal regions of the MCA territory and the ipsilateral cerebellum were defined. Using mean counts of 7 VOIs, cerebral perfusion index and perfusion reserve index were calculated. Results: Seventeen patients (M:F =12:5, mean age $53{\pm}2yr$) were finally included in the analysis. The cerebral blood flow of the parietal region increased at 1 week (p = 0.003) and decreased to the preoperative level at 3-6 months (p = 0.003). The cerebrovascular reserve of the frontal and parietal regions increased significantly at 1 week after surgery (p<0.01) and improved further at 3-6 months. Conclusion: Cerebrovascular reserve of the MCA territory was significantly improved at early postoperative period after EC-IC bypass and kept improved state during long-term follow-up, although cerebral blood flow did not significantly improved. Therefore, cerebrovascular reserve may be a good indicator of postoperative hemodynamic improvement resulted from bypass effect.

• The Journal of Internal Korean Medicine
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• v.42 no.1
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• pp.25-39
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• 2021

Objective: The purpose of this study was to investigate the effect of Lonicera Japonica Thunberg (LJT) on the inflammatory factor expression associated with atherosclerosis in human umbilical vein endothelial cells (HUVECs). Methods: After treatment with LJT in HUVEC which is treated with TNF-α, we measured the expression levels of biomarkers (MCP-1, ICAM-1, VCAM-1, KLF2, and eNOS), mRNA (CCL2, ICAM1, VCAM1, KLF2, and NOS3), and the proteins (MCP-1, ICAM-1, VCAM-1, KLF2, eNOS, ERK, JNK, and p38). Results: 1. Compared to the control, LJT significantly reduced MCP-1 and VCAM-1 levels at concentrations of 100, 200, and 400 ㎍/ml and ICAM-1 expression at 200 and 400 ㎍/ml compared to the control. It increased KLF2 levels at all three concentrations, but not significantly, while eNOS expression was significantly increased at 400 ㎍/ml. 2. LJT was seen to significantly reduce the expression of CCL2, ICAM1, and VCAM1 mRNA at concentrations of 100, 200, and 400 ㎍/ml compared to the control. In contrast, significantly increased KLF2 and NOS3 mRNA levels were observed at 400 ㎍/ml and at 200 and 400 ㎍/ml, respectively. 3. Compared to the control, LJT significantly reduced the protein expression of MCP-1 and VCAM-1 at 200 and 400 ㎍/ml and of ICAM-1 at 400 ㎍/ml. In addition, it increased both KLF2 and eNOS protein levels at 200 and 400 ㎍/ml. Although LJT did not have an effect on ERK expression in comparison with the control, it significantly reduced JNK levels at 200 and 400 ㎍/ml and p38 levels at 400 ㎍/ml. Conclusions: These results suggest that LJT has an effect on the inhibition of inflammatory factor expression associated with atherosclerosis in HUVECs which could contribute to the prevention of cardiovascular and cerebrovascular diseases.