• Title/Summary/Keyword: Atherosclerosis

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Characterization of Matrix Metalloproteinase Expression in Triglyceride Treated THP-1 Macrophages

  • Cho, Yoonjung;Lim, Jaewon;Lee, Dong Hyun;Jung, Byung Chul;Lee, Min Ho;Jung, Dongju;Kim, Yoon Suk;Kim, Tae Ue;Rhee, Ki-Jong
    • Biomedical Science Letters
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    • v.19 no.1
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    • pp.9-16
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    • 2013
  • Elevated blood triglyceride (TG) levels correlate with development of atherosclerosis suggesting that TG may promote the development of this disease. During atherosclerosis, TG is taken up by tissue macrophages which result in dramatic changes in various secreted factors. One such factor is the family of matrix metalloproteases (MMP) which are involved in tissue remodeling during both physiological and pathological processes. In this study, we examined the MMP expression profile in PMA-differentiated THP-1 macrophages treated with TG. We found that TG-treated THP-1 macrophages showed decreased expression of MMP-3, MMP-7, MMP-8 and MMP-9 in a time- and dose-dependent manner. In contrast, expression of MMP-1, MMP-2, and MMP-10 remained relatively unchanged after TG treatment. In addition, we found that expression of select MMPs was affected by various inhibitors of signaling pathways. In particular, expression of MMP-3 was slightly recovered by cRAF and PLC signaling pathway inhibitors. These data suggests a possible role of MMPs in macrophages during TG-induced atherosclerosis.

Study on the Curative Effects of the Semyung-Gangji-tang on the Atherosclerosis in Hyperlipidemic Rabbits (세명항지탕이 토끼의 죽상동맥경화증에 미치는 영향)

  • 김규열;서일복
    • 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.

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Influence of Cardiac Contraction and its Phase Angle with Coronary Blood flow on Atherosclerosis of Coronary Artery (심장의 수축운동과 관상동맥 혈류와의 위상차가 관상동맥 혈관의 동맥경화 민감성에 미치는 영향)

  • 김민철;이종선;김찬중;권혁문
    • Journal of Biomedical Engineering Research
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    • v.23 no.6
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    • pp.437-449
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    • 2002
  • Coronary arteries are subjected to very different flow conditions compared to other arteries in systemic blood circulation. We Performed a computational fluid dynamic research to investigate influence of such flow conditions in coronary arteries on development and progress of atherosclerosis in the same. The results showed big differences in the flow field of the coronary artery compared to the abdominal and femoral arteries. The coronary artery showed higher wall shear stresses due to the small vessel diameter. On the other hand, it showed only one vortex distal to the stenosis throat during a whole pulse cycle. However. several vortices were observed in the abdominal and femoral arteries in both proximal and distal sides of the stenosis throat The wall shear stresses and extent of recirculation area were increased with impedance phase angle increasing toward more negative values. Therefore, cardiac contraction and the negative impedance phase angle as large as -110。 may induce a flow field that accelerates atherosclerosis.

Inhibitory Effects of A-8 on Abnormal Rat Aortic Vascular Smooth Muscle Cell Proliferation (동맥혈관 평활근세포 증식에 대한 오보바톨 유도체(A-8)의 억제효과)

  • Lim, Yong;Lee, Mi-Yea;Tudev, Munkhtsetseg;Park, Eun-Seok;Jung, Jae-Kyung;Yun, Yeo-Pyo
    • YAKHAK HOEJI
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    • v.55 no.2
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    • pp.116-120
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    • 2011
  • Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of proliferative cardiovascular diseases, including hypertension and atherosclerosis. To find antiproliferative agent (A)-8 had inhibitory effect on VSMCs proliferation. Therefore, we examined the antiproliferative effect of A-8, a newly synthesized obovatol derivative. To investigate the antiproliferative effect of A-8, we examined cell counting and [$^3H$]-thymidine incorporation assays. The pre-incubation of A-8 (1~4 ${\mu}M$) significantly inhibited proliferation and DNA synthesis of 5% fetal bovine serum (FBS)-stimulated rat aortic VSMCs in concentration-dependent manner. Whereas, A-8 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. In addition, A-8 significantly inhibited 5% FBS-induced cell cycle progression in rat aortic VSMCs. These results show that A-8 may be developed as a potential antiproliferative agent for treatment of angioplasty restenosis and atherosclerosis. Furthermore, A-8 should be examined for further clinical application either as a single agent or in combination with other angioplasty restenosis or atherosclerosis agents.

Atherogenic Risk Stratification According to Changes in the Geometrical Shape of the Coronary Artery (관상동맥의 기하학적 형상변화에 따른 동맥경화 위험도)

  • Suh, Sang-Ho;Park, Jun-Gil;Roh, Hyung-Woon;Lee, Byung-Kwon;Kwon, Hyuck-Moon
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.34 no.10
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    • pp.893-899
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    • 2010
  • A previous study showed that hemodynamics is correlated with stenosis in the coronary artery. The flow characteristics and the distributions of the hemodynamic wall parameters in the coronary artery are investigated under physiological flow condition. The present study also aims to establish the mechanism of the generation of atherosclerosis by analyzing the hemodynamic variables in the coronary artery where atherosclerosis frequently occurs. The stenosis phenomena due to atherosclerosis are related to not only the biochemical reaction between blood and blood vessels but also the hemodynamic factors sush as flow separation and oscillatory wall shear stress. As the bifurcated angle increases, the size of the recirculation area that appears in the cross section increases and disturbed flow is observed in this area. We speculate that this area is the starting point of atherosclerosis in the coronary artery.

The Stimulation of CD147 Induces MMP-9 Expression through ERK and NF-${\kappa}B$ in Macrophages: Implication for Atherosclerosis

  • Kim, Ju-Young;Kim, Won-Jung;Kim, Ho;Suk, Kyoung-Ho;Lee, Won-Ha
    • IMMUNE NETWORK
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    • v.9 no.3
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    • pp.90-97
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    • 2009
  • Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation. Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface. Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-${\kappa}B$. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of $I{\kappa}B$, and nuclear translocation of NF-${\kappa}B$ p65 and p50 subunits. Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

Influence of Panax notoginseng on the Atherosclerosis Induced by High-cholesterol Feed in Rats (고콜레스테롤 식이로 유발된 동맥경화병태흰쥐의 혈관조직내 지질과산화 및 산화스트레스에 대한 삼칠근의 영향)

  • Kim, Jong-Goo;Park, Sun-Dong;Park, Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1187-1195
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    • 2006
  • Panax notoginseng exhibit several beneficial effects including anti-oxidant effects. P. notoginseng is used as a therapeutic agent to stop haemorrhages and a tonic to promoted health in Korean and Chinese medicine. The pharmacokinetic profiles of the main P. notoginseng are still not accurately investigated. The exact mechanism of the anti-oxidant activitys of water extracts of P. notoginseng, however, has not been determined. in present study, I examined the effects of water extracts of P. notoginseng on high cholesterol diet atherosclerosis-induced rats in serum and abdominal aorta. A total of 3-week old 9 male rats of Sprague-Dawley were divided into 3 groups and fed with the basal diet (normal group), high cholesterol diet (atherosclerosis induced group) for 8 weeks, high cholesterol diet supplemented with water extracts of P. notoginseng (P. notoginseng group) for 4 weeks. And rats were sacrificed, serum lipid level, abodominal aortic anti-oxidant activities and lipid peroxide were measured. These results indicated that serum total cholesterl, LDL-cholesterol, triglycerides concentration significently lowered in P. notoginseng group than high cholesterol diet group. But HDL-cholesterol concentraion significently higher in P. notoginseng group than high cholesterol feed group. And abdominal aortic xanthine oxidase activity was significantly reduced by dietary water extracts of P. notoginseng supplementation (p<0.05) Also abdominal aortic superoxide dismutase, catalase, glutathione peroxidase activities were significantly increased by dietary water extracts of P. notoginseng supplementation (p<0.05) Especially, abdominal aortic level of lipid peroxide tended to increase in high cholesterol feed group, but water extract of P. notoginseng intake reduced the value (p<0.05).

Effects of Antioxidant and Anti-inflammatory Activity of Allii Macrostemonis Bulbus Cheonghyeol Plus on the Inhibition of Atherosclerosis (해백청혈플러스(AMCP)의 항산화 및 항염증 작용을 통한 죽상동맥경화 억제 효과)

  • Chae, Incheol;Ryu, Juyeong;Yoo, Horyong;Kim, Yoonsik;Seol, Inchan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.3
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    • pp.126-135
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    • 2020
  • The purpose of this study was to investigate the antioxidant, anti-inflammatory and anti-cellular adhesion molecules effects of Allii Macrostemonis Bulbus, Artemisiae Capillaris Herba, Curcumae Radix, Crataegi Fructus, Salviae Militiorrhizae Radix complex extract(AMCP) on the inhibition of atherosclerosis in HUVEC. We measured DPPH radical scavenging activity and ABTS radical scavenging activity of AMCP to evaluate its antioxidant effect. And we also measured the expression level of NF-κB, IκBα, ERK, JNK, p38 proteins to evaluate its anti-inflammatory effect. Lastly, we measured the expression level of MCP-1, ICAM-1, VCAM-1 mRNA and their level to evaluate its anti-celluar adhesion molecules. AMCP did not show any cytotoxicity in HUVEC within the concentraion tested except for a concentration of 400 ㎍/㎖. AMCP increased the DPPH radical scavenging activitiy and ABTS radical scavenging activity in HUVEC as the concentration of AMCP rises. AMCP significantly reduced NF-κB, IκBα, JNK, ERK and p38 protein expression in HUVEC compared to control group. AMCP significantly reduced MCP-1, ICAM-1, VCAM-1 gene expresion in HUVEC compared to control group. AMCP significantly decreased the levels of MCP-1, ICAM-1, VCAM-1 in HUVEC compared to control group. These results suggest that AMCP has effects on antioxidation, anti-inflammation and anti-cellular adhesion molecule, which helps the treatment and prevention of dyslipidemia and atherosclerosis.

Feasibility Study on RI Biochip Application to Detection of Risk Factors of Atherosclerosis (RI검출 바이오칩의 혈관계 질환 발생 위험인자 검지에 대한 타당성 연구)

  • Ko, Kyong-Cheol;Choi, Mi Hee;Park, Sang Hyun;Cho, Kyung-Hyun;Lee, Ki-Teak
    • Journal of Radiation Industry
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    • v.3 no.1
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    • pp.25-29
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    • 2009
  • Microarrays can be used to screen thousands of binding events in a parallel and high throughput fashion and are of major importance in disease diagnosis and drug discovery. The use of radioisotope is conventionally regarded as one of the most sensitive detection methods. Atherosclerosis is a common disorder affecting arterial blood vessels. It happens when fat, cholesterol, and other substances made in the arterial blood vessels form a hard substances called plaque. Lipoprotein-associated phospholipase $A_2$ ($Lp-PLA_2$), a phospholipase $A_2$ enzyme, is used as a marker for cardiac disease. The detection of $Lp-PLA_2$ was accomplished by using radioactive [$^3H-acetyl$] PAF as a substrate and a feasibility study on RI biochip application to detection of $Lp-PLA_2$, a risk factors of atherosclerosis was performed. Inhibitive activity of a native plant extract was also determined by using the RI biochip. It was found to be applicable to a high-throughput screening of inhibitors for developing atherosclerosis therapeutic agents.

Extract of Curcuma zedoaria R. prevents atherosclerosis in apolipoprotein E-deficient mice

  • Kim, Ki Mo;Lee, Joo Young;Jeon, Byeong Hwa;Quan, Khong Trong;Na, MinKyun;Nam, Kung-Woo;Chae, Sungwook
    • Nutrition Research and Practice
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    • v.15 no.3
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    • pp.319-328
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    • 2021
  • BACKGROUND/OBJECTIVES: Curcuma zedoaria R. (Zingiberaceae) has been used to treat headache, fever, and hypertension-related symptoms in Asian countries, including Korea, China, and Japan. We investigated whether dietary intake of a C. zedoaria extract (CzE) affected atherosclerosis in vivo. MATERIALS/METHODS: Apolipoprotein E-deficient (ApoE-/-) mice (n = 32) were fed a normal diet (ND), a high-cholesterol diet (HCD), an HCD containing CzE (100 mg/kg/day), or an HCD containing simvastatin (10 mg/kg/day) for 12 weeks. The anti-atherosclerotic effects were evaluated by observing changes in fatty streak lesions, immunohistochemical analysis, ex vivo fluorescence imaging, lipid profiles, and western blot analysis. RESULTS: The CzE-fed group showed a 41.6% reduction of atherosclerosis. Furthermore, CzE significantly reduced the levels of serum triglyceride, high-density lipoprotein, the chemokine (C-X3-C-motif ) ligand 1, the adhesion molecules vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin; down-regulation of tumor necrosis factor-α, interleukin-6, high mobility group box-1, and cathepsin levels in the aortic sinuses and aortas of ApoE-/- mice were also observed. CONCLUSIONS: The results suggest that the inclusion of a water extract of C. zedoaria in a HCD is closely correlated with reducing the risk of vascular inflammatory diseases in an ApoE mouse model.