• 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.

• Korean Journal of Clinical Pharmacy
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• v.12 no.1
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• pp.39-50
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• 2002

Hypercholesterolemia is one of main causes of coronary heart disease(CHD). Clinical trials demonstrated that lowering serum cholesterol levels would reduce incidence of new cardiovascular events and mortality by primary or secondary preventions. The objective of this retrospective study was to compare efficacy and side effects of lovartatin and simvastatin in treatement of hypercholesterolemia. In Boramae Hospital, patients were included when they have taken lovastatin 20 mg or simvastatin 10 mg for 52 weeks with laboratory monitoring for cholesterol at baseline, 3, 6 and 12 month period. As results, total 128 outpatients were included with their total cholesterol level <240 mg/dl and triglyceride level <400 mg/dl at baseline. Total cholesterol and LDL cholesterol of lovastatin group (n=60) and simvastatin group (n=68) were significantly reduced from baseline (p=0.001). Lovastatin maximally reduced total cholesterol by $23.9\%,\;triglyceride\;by\;12.3\%$, LDL cholesterol by $36.1\;\%$ and increased HDL cholerterol by $7.8\%$ and simvastatin reduced by $24.1\%,\;20.5\%,\;34.3\%\;respectively$ and HDL increased by $11.2\%$. There were no significant differences between lovastatin and simvastatin in mean percent change of lipid levels at 12, 24 and 52 weeks from baseline. Cumulative percentage of patients reaching the target LDL cholesterol concentration by 24 weeks was $61.7\%$ in lovastatin and $64.7\%$ in simvastatin. Average time to reach the target LDL goal was 100.1 days in lovastatin and 99.8 days in simvastatin. Both lovastatin and simvastatin also significantly reduced total cholesterol and LDL cholesterol in all subgroups (diabetes mellitus, hypertension, and coronary heart disease). In this study, treatment efficacy in patients with coronary heart disease was lower than other patients. Considering clinical importance of secondary prevention, more intensive treatment is necessary to decrease LDL cholesterol level of 100 mg/dl or lower in patients with coronary heart disease or other clinical atherosclerotic disease. There were no serious side effects during the study period. Digestive side effects were most frequently reported (lovastatin $8.3\%\;vs\;simvastatin\;8.8\%$). In conclusion, both lovastatin and simvastatin were similar in lipid lowering effects and there was no difference in incidence of side effects.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.229-234
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• 2015

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-${\alpha}$ for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogenactivated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM ($0.01{\sim}100{\mu}g/mL$) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-${\alpha}$ (3 ng/mL), and it dose dependently prevented the TNF-${\alpha}$ -induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-${\alpha}$ -induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-${\alpha}$ -induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

• Korean Journal of Radiology
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• v.21 no.9
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• pp.1055-1064
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• 2020

Objective: To assess the incremental prognostic value of coronary computed tomography angiography (CCTA) in comparison to a clinical risk model (Framingham risk score, FRS) and coronary artery calcium score (CACS) for future cardiac events in ischemic stroke patients without chest pain. Materials and Methods: This retrospective study included 1418 patients with acute stroke who had no previous cardiac disease and underwent CCTA, including CACS. Stenosis degree and plaque types (high-risk, non-calcified, mixed, or calcified plaques) were assessed as CCTA variables. High-risk plaque was defined when at least two of the following characteristics were observed: low-density plaque, positive remodeling, spotty calcification, or napkin-ring sign. We compared the incremental prognostic value of CCTA for major adverse cardiovascular events (MACE) over CACS and FRS. Results: The prevalence of any plaque and obstructive coronary artery disease (CAD) (stenosis ≥ 50%) were 70.7% and 30.2%, respectively. During the median follow-up period of 48 months, 108 patients (7.6%) experienced MACE. Increasing FRS, CACS, and stenosis degree were positively associated with MACE (all p < 0.05). Patients with high-risk plaque type showed the highest incidence of MACE, followed by non-calcified, mixed, and calcified plaque, respectively (log-rank p < 0.001). Among the prediction models for MACE, adding stenosis degree to FRS showed better discrimination and risk reclassification compared to FRS or the FRS + CACS model (all p < 0.05). Furthermore, incorporating plaque type in the prediction model significantly improved reclassification (integrated discrimination improvement, 0.08; p = 0.023) and showed the highest discrimination index (C-statistics, 0.85). However, the addition of CACS on CCTA with FRS did not add to the prediction ability for MACE (p > 0.05). Conclusion: Assessment of stenosis degree and plaque type using CCTA provided additional prognostic value over CACS and FRS to risk stratify stroke patients without prior history of CAD better.

• Journal of Acupuncture Research
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• v.19 no.3
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• pp.126-137
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• 2002

Objective : There is accumulating data that cardiovascular diseases, including hypertension, cerebro-vascular accident, coronary heart disease, relate to atherosclerotic changes. Increased serum levels of lipids could play a role in these circumstances. the SDPTG(the second derivative of photoplethysmogram waveform) is noninvasive methods for evaluating the pulse wave and is correlated with age and other risk factors for atherosclerosis. Methods : To study the effects of serum lipid levels on the SDPTG in the middle-age adults, data on serum lipid levels and the SDPTG were collected in 80 healthy middle age with varying serum lipid concentrations. Biological vascular age was assessed using the SDPTG. the SDPTG consists of an a, b, c, and d wave in systole and an e wave in diastole; an SDPTG aging index(Al) was calculated as (b-c-d-e)/a. Results : Serum triglyceride, total cholesterol, total lipid, phospholipid, HDL cholesterol levels were respectively and significantly correlated with SDPTG Al. Serum lipid levels and blood pressure are age-dependent and the SDPTG is blood pressure-dependent. Restricting analysis to age and blood pressure yield strong positive correlations between serum triglyceride, total lipid levels and SDPTG Al, but no correlations between serum total cholesterol, phospholipid levels and SDPTG Al. Conclusion : The results of this study suggest that preventive acupuncture programs or herbal medications for reducing serum lipid, especially triglyceride, levels in middle-age should include a evaluation of biological vascular aging with the second derivative of photoplethysmogram waveform.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.293-299
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• 2018

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) effectively reduce serum levels of low-density lipoprotein (LDL) and total cholesterol. High-intensity statins are recommended for all patients aged ${\leq}75$ with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus aged 40-75 with ${\geq}7.5%$ estimated 10-year ASCVD risk and LDL-C ${\geq}190mg/dL$. High-intensity statins associated with more frequent adverse events (AEs) compared to moderate- to low-intensity statins. The aim of this study was to compare AEs between high-intensity and moderate- to low-intensity statin group using the Korea Adverse Event Reporting System (KAERS) database. Methods: Adults (${\geq}18years$) with statin-associated AEs from July 2009-June 2014 were included. Only AEs classified as "certain", "probable" and "possible" based on the WHO-Uppsala Monitoring Center criteria were analyzed. Results: In total, 247 AEs from 196 patients [high-intensity statin group (HG), n = 25 (13%); moderate- to low-intensity statin group (MLG), n = 171 (87%)] were included. Mean age was higher in HG compared with MLG ($67{\pm}14$ vs $62{\pm}12$). The HG showed a significant higher frequency of liver/biliary system disorders (37% vs 14%, p = 0.001). Hepatic function abnormal was reported more frequently in HG compared to MLG (26% vs 9%, p = 0.006). Conclusion: According to KAERS data, liver/biliary system disorders were more frequently reported in HG compared to MLG.

• BMB Reports
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• v.56 no.8
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• pp.445-450
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• 2023

The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatment of HASMCs with full-length recombinant human HAPLN1 (rhHAPLN1) significantly reversed PDGF-BB-induced decrease in the protein levels of contractile markers (SM22α, α-SMA, calponin, and SM-MHC), and inhibited the proliferation and migration of HASMCs induced by PDGF-BB. Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. Together, these results indicated that rhHAPLN1 can suppress the PDGF-BB-stimulated phenotypic switching and subsequent de-differentiation of HASMCs, highlighting its potential as a novel therapeutic target for atherosclerosis and other vascular diseases.

• Journal of Chest Surgery
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• v.42 no.1
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• pp.53-58
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• 2009

Background: The goal of this study was to compare the patency and complications of femoropopliteal bypass with superficial femoral artery stenting for patients with atherosclerotic superficial femoral artery occlusive disease. Material and Method: Between July 2005 and July 2008, we reviewed 29 femoropopliteal bypass procedures (24 patients) with prosthetic grafts (the bypass group) and 19 superficial femoral artery stentings (15 patients) with nitinol stent (the stent group). There were 35 male patients (89.7%) and the mean age of the patients was 69.2 years (range: 48~84). The number of patients who had DM, hypertension and a smoking history was 25 patients (64.1%), 17 patients (43.6%) and 30 patients (76.9%), respectively. 23 (59.0%) patients had skin ulceration or tissue gangrene at admission. Result: There were 27 cases (93.0%) of TASC C&D lesion in the bypass group and 16 cases (84.2%) of TASC A&B lesion in the stent group. There were significant differences for the indications for a procedure between the two groups (p<0.01). The primary patency rates at 6 months, 12 months and 24 months were 91.9%, 79.7% and 79.7% for the bypass group and 93.3%, 86.2% and 86.2% for the stent group, respectively. There were no statistical difference between the two groups (p=0.48). Conclusion: There were no significant differences in the outcome between two groups. TASC C&D lesion and failed intervention therapy should be treated with femoropopliteal bypass surgery, and TASC A&B lesion and the high-risk patients should be treated with femoral artery stent insertion.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.4
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• pp.280-286
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• 2016

Polyphenols have been reported to have beneficial effects on cardiovascular disease. A polyphenolic compound, 3,4-dihydroxy-hydrocinnamic acid (3,4-DHHCA), has been shown to have antioxidative and antitumorigenic activities. However, the effect of 3,4-DHHCA on atherosclerosis is still unknown. Herein, we investigated the effects of 3,4-DHHCA on atherosclerosis in New Zealand White rabbits. Broad and fused fatty streak lesions were found in rabbits fed with high-cholesterol diet for 8 weeks. Administration of 3,4-DHHCA reduced atherosclerotic lesion formation and lesional accumulation of macrophage in rabbits fed with cholesterol diet without systemic or local toxicity. Hepatic acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity was decreased after treatment with 3,4-DHHCA by 22% in cholesterol diet-fed rabbits compared with the control group. These results indicate that 3,4-DHHCA had antiatherogenic effects in rabbits, possibly by partial inhibition of ACAT.

• Journal of Chest Surgery
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• v.34 no.10
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• pp.787-791
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• 2001

Coronary artery aneurysm is a rare disorder. It is defined as abnormal dilatation of coronary artery with diameter exceeding 1.5 times the adjacent normal segments. The incidence of coronary aneurysm is 2.6% in Caucasians and 0.25% in Asians. Over half of the former were associated with atherosclerotic coronary artery disease. However, 70 percents of the latter were nonobstructive coronary artery aneurysms. Coronary artery fistula is a rare disorder. It has been identified in only 0.2% of routine cardiac angiographic studies conducted over a 10-year period. The clinical spectrums are various, asymtomatic, asymptomatic murmur, dyspnea on exertion, fatigue, and congestive heart failure. The right coronary artery (56%) and left coronary artery(36%) are mainly involved in the origin site of congenital coronary artery fistula. The draining site of fistula are right ventricle(39%), right atrium(33%), and pulmonary artery(20%) and so on. This 54 years-old woman had intermittent chest tightness and an abnormal mediastinal shadow on chest roentgenogram and chest C-T examination, which was diagnosed as a mediastinal mass such as teratoma. We performed the operation under left anterolateral thoracotomy for mass excision. However, we knew the mass had the pulsating arterial blood flow through a fine needle puncture of the mass and that it was attached to the left ventricle. We believed the excision of mass on beating heart would be very dangerous. Therefore, we closed the wound without excising the mass. After several days, we performed an echocardiography and coronary angiography, We knew it was cardiac tumor. Incidentally, the patient had a tortuous coronary fistula from the right coronary artery to pulmonary trunk. Using cardiopulmonary bypass with moderate systemic hypothermia, the mass was resected and the fistula was clipped with surgical clips. Pathology of the specimen was a giant coronary arterial aneurysm.