( 您好!臺灣時間:2024/02/29 13:43
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::


研究生(外文):Mei-Ling Li
論文名稱(外文):High Molecular Protocatechuic Acid Polymers Induces Atherosclerosis and NF-κB Activation
指導教授(外文):Hsin-Ling Yang
外文關鍵詞:High molecular Protocatechuic acid polymerBlackfoot diseaseAtherosclerosisNuclear factor-kappa B
  • 被引用被引用:0
  • 點閱點閱:271
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
高分子原兒茶酸(腐植酸)已被證實為台灣西南沿海烏腳病的致病因子之ㄧ。在本篇研究中,我們探討腐植酸誘導動脈粥狀硬化及活化轉錄因子NF-κB之機制。在動物實驗結果發現,腐植酸可以誘導動脈粥狀硬化的發生,而此情形並不是經由增加血漿中的膽固醇及三酸甘油脂。在體外試驗中發現,腐植酸會(1)促進人類臍帶內皮細胞黏附因子(例如:ICAM-1、VCAM-1)以及COX-2蛋白質表現;(2)促進鼠類巨噬細胞RAW 264.7細胞株COX-2、iNOS、L-1β、TNF-α、PGE2 以及NO的釋放;(3)並會促進A7r5大鼠平滑肌細胞株MMP-9、PDGF-A以及COX-2蛋白質表現。而NF-κB訊息傳遞路徑在這些表現的機制上扮演重要的角色。因此我們可以知道,腐植酸會促進烏腳病患者的動脈粥狀硬化發生,在此其中NF-κB為此疾病病因發生的主要因子之ㄧ。
High molecular Protocatechuic acid polymer (humic acid, HA) have been implicated as an etiological factor of Blackfoot disease (BFD) endemic in the southwest coast of Taiwan. In this study, we investigated the effect of HA on atherosclerosis and activation of nuclear factor – kappa B (NF-κB). In animal study, we suggest HA can increase the atherosclerosis. This increase was not due to increasing in serum cholesterol and triacylglycerol (TG). In vitro study, HA was shown to enhance (1) activation of adhesion molecular (ex: intercellular cell adhesion molecule-1, ICAM-1; vascular cell adhesion molecule-1, VCAM-1) and COX-2 in human umbilical vein endothelial cells; (2) expression of cyclooxygenase-2 (COX-2), induce nutric oxide synthase (iNOS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and nutric oxide (NO) in RAW264.7 macrophage cell line; (3) activation of matrix metalloproteinase (MMP-9), platelet derived growth factor-A (PDGF-A), and COX-2 in A7r5 rat smooth muscle cell line. NF-κB signal pathway play an important role in the mechanism. In conclusion, HA may increase the atherosclerosis, occurs for patients with blackfoot disease, NF-κB may be a critical molecular in the pathogenesis of this disease.
前言----------------------------------------------- 5
實驗目的----------------------------------------- 30
實驗方法 ---------------------------------------- 31
動物實驗部份結果與討論--------------------- 57
1.腐植酸對於人類臍帶靜脈內皮細胞之影響--------- 65
2.腐植酸對於小鼠巨噬細胞株RAW 264.7之影響-- 77
3.腐植酸對於A7r5大鼠平滑肌細株胞之影響-------- 92
結論------------------------------------------------- 101
1.Prakash, A. and MacGregor, D. J. Environmental and human health significance of humic materials: an overview. In: Christman, R. F. and Gjessing, E. T. (Eds) Aquatic and Terrestrial Humic Materials. Ann Arbor Science, Ann Arbor, Michigan. 1983, 481-94.
2.Hatcher, H., Hedges, R. E. M., Pollard, A. M., and Kenrick, P. M. Analysis of Hellenistic and Roman fine pottery from Benghazi. Archaeometry. 1980, 22, 133–51.
3.Aiken, G. R., McKnight, Diane, M., Wershaw, Robert, L. and Patrick, M. Humic substances in soil, sediment, and water; geochemistry, isolation, and characterization. John Wiley & Sons ; New York. 1985
4.P. MacCarthy, C. E. Clapp, R. L. Malcolm and R. R. Bloom, ‘Humic Substances in Soil and Crop Sciences: Selected Readings’, American Society of Agronomy, Madison, Wisconsin, 1990.
5.Stevenson, F.J. Humus Chemistry:Genesis, Composition and Reactions. Wiley, New York. 1982
6.Hayes, M. H. B., MacCarthy, P., Malcolm, R. L. and Swift R. S. ‘Humic Substances II: In Search for structure’. Wiley, Chichester. 1989.
7.Ziechmann, W. ‘Humic Substances’. BI Wissenschaftsverlag, Mannheim. 1993.
8.Senesi, N. and Miano, T. M. ‘Humic Substances in the Global Environment: Implications for Human Health’. Elsevier, Amsterdam. 1994.
9.Stevenson, F. J. ''Humus Chemistry: Genesis, Composition, Reactions''. 2nd edn., Wiley, New York. 1994.
10.Gaffney, J. S., Marley N. A. and Clark, S. B. ‘Humic and Fulvic Acids: Isolation, Structure and Environmental Role’. American Chemical Society Symposium Series 651. 1996.
11.Hayes M. H. B. and Wilson, W. S. ''Humic Substances, Peats and Sludges: Health and Environmental Aspects''. Royal Society of Chemistry, Cambridge. 1997.

12.Davies, G. and Ghabbour, E. A. ‘Humic Substances: Structures, Properties and Uses’. Royal Society of Chemistry, Cambridge. 1998.
13.Stott, E.T. and Martin, J. P. Synthesis and degradation of natural and synthetic humic material in soils. American Society of Agronomy, Soil Science Society of America, Inc. Madison, Wisconsin, USA. 1990, 37-64.
14.Hayes, M. H. B. Humic substances II. A Wiley-Interscience publication press. 1989.
15.Schnitzer, M. Recent Findings on the Characterization of Humic Substances extracted from soils from widely differing climatic zones. In: Proceedings of the Symposium on Soil Organic Matter Studies, Braunschweig, International Atomic Energy Agency, Vienna. 1977, 117–131.
16.Steelink, C.Free radical studies of lignin, lignin degradation products and soil humic acid. Geochim. Cosmochim. Acta. 1964, 28:1615–1622.
17.Steelink, C. Implications of elemental characteristics of humic substances. In G.R. Aiken et al. (ed.) Humic substances in soil, sediment, and water Geochemistry, isolation, and characterization. John Wiley & Sons, New York. 1985, 457-476
18.Lundquist, J.B. A primer on limnology.. University of Minnesota Water Resources Research Center, Public Report Series. 1975.
19.Frankel, E. N., Eaterhouse, A. L., Kinsella, J. E. Inhibition of human LDL oxidation by resveratrol. Lancet. 1993, 341: 1103.
20.Kerry, N. L. and Abbey, M. Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro. Atherosclerosis. 1997, 135: 93.
21.Maxwell, S., Cruickshank, A., Thorpe, G. Red wine and antioxidant activity in serum. Lancet. 1994, 344: 193.
22.Fuhrman, B., Buch, S., Vaya J. Licorice extract and irs major polyphenol glabridin protect low-density lipoprotein against lipid peroxidation: in vitro and ex vivo studies in humans and in athersclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 1997, 66: 267.
23.Halevy, D., Thiery, J., Nagel, D. Incresed oxidation of LDL in patients with coronary artery disease is independent from dietary vitamins E and C. Arterioscler Thromb Vasc Biol. 1997, 17: 1432.
24.Tanaka, T., Kojima, T., Kawamori, T. Chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis by a simple phenolic acid, protocatechuic acid in rats . Cancer Res. 1993, 53:2775 .
25.Tanaka, T., Kawamori, T., Ohnishi, M. Chemoprevention of 4-nitroquinoline 1-oxide-induce oral carcinogenesis by dietary protocatechuic acid during initiation and postinitiation phases. Cancer Res. 1994, 54: 2359.
26.Kawamori, T., Tanaka, T., Kojima, T. Suppraession of azoxymethane-inducedrat colon aberrant crypt focal by dietary protocatechuic acid. Jpn J Cancer Res. 1994, 85: 686.
27.Nomura, A. M. Y., Kolonel, L. N., Hankin J. H., Yoshizawa C. N. Dietary factors in cancer of the lower urinary trace. Int J Cancer. 1991, 48:199.
28.Hung, M., Ferrano, T. Phenolic compounds in food and cancer prevention. In Huang MT, Ho CT, Lee CY. (eds). Phenolic compounds in Food and Their Effects on Health H: Antioxidants and Cancer prevention. American Chemical Society Symposium Series 507, American Chemical Society, Washington, DC. 1992, 8-34.
29.Nakamura, T., Nakauawa, Y., Onizuka S. Antimutagenicity of Tochu tea (an aqueous extract of Eucommia ulmoides leaves). The clastogen-suppressing effects of Tochu tea in CHO cells and mice. Mutat Res. 1995, 388: 7.
30.Paya, M., Ferrandiz, F., Miralles C. Effects of counarin derivatives on superoxide anion generation. Arzneimittel Forsch. 1993, 43: 655-661.
31.Hiramoto, K., Ojima, N., Sako, K.I., and Kikugawa, K. Effect of plant phenolics on the formation of the spin-adduct of hydroxyl radical and the DNA strand breaking by hydroxyl radical. Biol Pharm Bull. 1996, 19:558-563.

32.Gaitan, E., Jolly, R. L., Lee, N. E., Lindsay, R. J., Cooksey, R. C., Hill, J. R., Kelly, K. Phthalate ester: Possible progoitrogens in water supply of a Colombia district withendemic goiter. J Am Chem Soc. 1983, 23:175-178.
33.Cookesy, R. C., Gaitain, E., Lindsay, R. J., Hill, J.R., Keely, K. Humic substances, a possible source of environmental goitrogens. Org Geochem. 1985, 8:77-80.
34.Gaitan, E., Medina, T.A., Zia, M. S. Goiter prevalence and bacterial contamination of water supply. J Clin Endocrinol Methab. 1980, 51:957-962.
35.Lu, F. J., Guo, H., Chiangs, H. S., Hong, C. L. Relationships between the fluorescent intensity of well water and the incidence rate of bladder cancer. J Chinese Oncol Soc. 1986, 2:14.
36.Lu, F. J., Yamamura, Y., Yamauchi, H. Studies on flurescent compounds in water of a well in Blackfoot disease endemic areas in Taiwan: Humic substances. J Formosan Med Assoc. 1988, 87:66-75.
37.Zhai, S. S., Kimbrough, R. D., Meng, B., Han, J. Y., Levoid, M., Hou, X., Yin, X. N., Kashin-Beck disease: A cross-sectional study in seven villages in the Peoples’ Republic of China. J Toxicol Environ Health. 1990, 30:239-259.
38.Huang, T. S., Lu, F. J. and Tsai, C. W. Tissue distribution of absorbed humic acids. Environ Geoche Health. 1995, 17:1-4.
39.Hseu, Y. C., Lu, F. J., Engelking, L. R., Chen, C. L., Chen, Y. H., Yang, H. L. Humic acid-induced echinocyte transformation in human erythrocytes: characterization of morphological changes and determination of the mechanism underlying damage. J Toxi Environ Health. 2000, 60:215-30.
40.Hseu, Y. C., Wang, S. Y., Chen, H. Y., Lu, F. J., Gau., R. J., Chang, W. C., Liu, T. Z., Yang, H. L. Humic acid induces the generation of nitric oxide in human umbilical vein endothelial cells: stimulation of nitric oxide synthase during cell injury. Free Radi Bio Med. 2002, 32:619-29.

41.Lee, Y., Huang T. S., Yang, M. L., Huang, L. R., Chen, C. H., Lu, F. J. Peroxisome proliferation, adipocyte determination and differentiation of C3H10T1/2 fibroblast cells induced by humic acid: Induced of PPAR in diverse cells. J. Cell. Physiol. 1999, 179: 218-225.
42.Yang, M. L., Huang, T. S., Lee, Y., Chen, T. H., Chen, S. Y. and Lu, F. J. Inhibition of endogenous thyroid hormone receptor- β and peroxisome proliferation-activated receptor-α activities by humic acid in a human-derived liver cell line. Thyroid. 2002, 12:361-371.
43.Yang, M. L., Lee, Y., Huang, T. S. and Lu, F. J. Humic acid extracted from blackfoot disease-endemic well water induces adipocyte differentiation of C3H10T1/2 fibroblast cells: a possible mechanism leading to atherosclerotic-like plaque in blackfoot disease. Arch Toxicol. 2002, 76: 48-54.
44.Huang, Y. L., Huang, T. S., Lu F. J. Humic acid induces the expression of ox-LDL receptor in HL-60 cells through activation of PPARr. Bulletin Environ. Contamin. and Toxicol. 2003, 71:429-436.
45.Gau, R. J., Yang, H. L., Chow, S. N., Suen, J. L., Lu F. J Humic acid suppresses the LPS-induced expression of cell-surface adhesion proteins through the inhibition of NF-κB activation. Toxicol Appl Pharmacol. 2000, 166:59-67.
46.Chen, C. H., Liu, J. J., Lu, F. J., Yang, M. L., Lee, Y, Huang, T. S. The effect of humic acid on the adhesibility of neutrophils (2003) Thrombosis Res. 2003, 108, 67-76.
47.Gau, R. J., Yang, H. L., Suen, J. L., Lu, F. J. Induction of oxidative stress by humic acid through increasing intracellular iron: a possible mechanism leading to atherothrombotic vascular disorder in blackfoot disease. Biochem. and Biophy. Research Commun. 2001, 283: 743-749.
48.Ho, K. J., Liu, T. K., Huang, T. S., Lu F. J. Humic acid mediates iron release from ferritin and promotes lipid peroxidation in vitro- a possible mechanism for humic acid induced cytotoxicity. Mol. Toxicol. 2003, 77: 100-109.
49.呂鋒洲、蔡孟慧、林國煌:烏腳病地區飲水中螢光物質之研究第一報--雞胚胎毒性實驗。臺灣醫學會雜誌。1977, 76:58-63。
50.Hofmanov??, J., Kozub?歸, A., Hol??, J., Sou?墈k, K., Kova???歸ov??, M., Zad?鴕, Z. Effect of sodium humate on the cell cycle and proliferation of mammalian cells. Klin Biochem Metab. 1999, 7:4-11.
51.Chen, Y. J., Lin-Chao, S., Huang, T. S., Yang, M. L., Lu, F. J. Humic acid induced growth retardation in a Sertoli cell line, TM4. Life Sci. 2001, 69:1269-1284.
52.Chen, J. Y., Lu, F. J., Ling, K. H. Studies on fluorescent compounds in drinking water of blackfoot disease endemic area. 5. Effects of fluorescent compounds on protein and nucleic acid synthesis in growing HeLa cells. Chinese J Microbiol. 1977, 10:115-117.
53.Lu, F. J., Tsai, S. C., Chen, J. Y. Studies on natural toxicants occurring in artesian well of blackfoot disease endemic area in Taiwan: chromosome aberrations in cultured lymphocytes exposed to fluorescent compounds. J Chinese Biochem Soc. 1980, 9:49-54.
54.Ribas, G., Carbonell, E., Creus, A., Xamena, N., Marcos, R. Genotoxicity of humic acid in cultured human lymphocytes and its interaction with the herbicides alachlor and maleic hydrazide. Environ Mol Mutagen. 1997, 29:272-276.
55.Bernacchi, F., Ponzanelli, I., Minunni, M., Falezza, A., Loprieno, N., Barale, R. In vivo cytogenetic effects of natural humic acid. Mutagenesis. 1996, 11:467-469.
56.呂鋒洲、劉東明。烏腳病患區飲水中螢光物質動物實驗模式。台灣醫誌。1986, 82:352-358。
57.Tseng, W. P., Chen, W. Y., Sung, J. L., Chen, J. S. A clinical study of blackfoot disease in Taiwan, an endemic peripheral vascular disease. Mem. Coll. Med Natl Taiwan Univ. 1961, 7:1-8

58.Yu, H. S., Sheu, H. M., Ko, S. S., Chiang, L. C., Chiene, C. H., Lin, S. M., Tserng, B. R., Chen, C. S. Studies on blackfoot disease and chronic arsenism in southern Taiwan : With special reference to skin lesions and fluorescent substances. J Dermatol. 1984, 11:361-370.
59.Tseng, W. P. Outcome of partients with blackfood disease. J. Formosan Med Assoc. 1975, 74:34-79.
60.Tseng, W. P. Effects and dose response relationship of shin cancer and blackfoot disease with arsenic. Environ Health Persp. 1977, 19:109-119.
61.余幸司、葛應欽、陳國熏。烏腳病致病機轉之探討-著重於砷及螢光物質對末梢血管內皮細胞的影響。烏腳病之研究報告。1989, 32:22-35。
63.呂鋒洲、劉東明。烏腳病地區飲水中之螢光物質之研究,螢光物與砷之關係。烏腳病之研究報告。1985, 22:24-43。
64.呂鋒洲、山村行夫、山內博。井水中螢光物質之研究—(三)台灣烏腳病患區一口井水中螢光物質之研究:腐植物質。烏腳病之研究報告。1988, 29:31-48。
65.呂鋒洲、董大成、林國煌。烏腳病地區飲用井水所含有機物質之鑑定。烏腳病之研究報告。1980, 8:1-9。
66.呂鋒洲、林信德、許隆隆。烏腳病地區地下水飲用水中螢光物質之在檢討。烏腳病之研究報告。1982, 12:1-15。
67.呂鋒洲、沈佩明。井水中螢光物質之研究—(二)烏腳病患區某伊井水中的化學至癌物質:辟瘟酸脂。烏腳病之研究報告。1988, 29:17-30。
68.Murray, C. J. and Lopez, A. D. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet. 1997, 349:1436–1442.
69.Ross, R. and Harker, L. Hyperlipidemia and atherosclerosis. Science. 1976, 193:1094–1100.

70.Hansson, G. K. Inflammation, Atherosclerosis, and Coronary Artery Disease. N Engl J Med. 2005, 352:1685-95.
71.Ross, R. Atherosclerosis – an inflammatory disease. N Engl J Med. 1999, 340:115-126.
72.Ross, R. Atherosclerosis is an inflammatory disease. Am Heart J. 1999, 138:S419-S420.
73.Libby, P., Ridker, P. M. Maseri, A. Inflammation and atherosclerosis. Circulation. 2002, 105:1135–1143.
74.Peter, Libby. Inflammation in atherosclerosis. Nature. 2002, 420:868-874
75.Piek, J. J., van der Wal, A. C., Meuwissen, M., Koch, K. T., Chamuleau, S. A., Teeling, P., van der Loos, C. M., Becker, A. E. Plaque inflammation in restenotic coronary lesions of patients with stable or unstable angina. J Am Coll Cardiol. 2000, 35:963-967.
76.Poole, J. C. F. and Florey, H. W. Changes in the endothelium of the aorta and the behavior of macrophages in experimental atheroma of rabbits. J Pathol Bacteriol. 1958, 75:245–253.
77.Kim, I., Moon, S. O., Kim, S. H., Kim, H. J., Koh, Y. S. and Koh, G. Y. Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and E-selectin through Nuclear Factor-kB Activation in Endothelial Cells. J Biol Chem. 2001, 276:7614–7620.
78.Gimbrone, M. A. In Molecular Cardiovascular Medicine. (Haber, E., ed) Scientific American Medicine, New York. 1995, 49-61.
79.Gimbrone, M. A., Nagel, T. and Topper, J. N. Biomechanical activation: an emerging paradigm in endothelial adhesion biology. J Clin Invest. 1997, 100:S61–S65
80.Bischoff, J. Cell adhesion and angiogenesis. J Clin Invest. 1997, 99:373–376
81.Johnson, R. C. Absence of P-selectin delays fatty streak formation in mice. J Clin Invest. 1997, 99:1037–1043.

82.Dong, Z. M. The combined role of P- and E-selectins in atherosclerosis. J Clin Invest. 1998, 2:145–152.
83.Glagov, S., Zarins, C., Giddens, D. P. and Ku, D. N. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med. 1988, 112:1018-1031.
84.Gu, L. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low-density lipoprotein-deficient mice. Mol Cell. 1998, 2:275–281.
85.Boring, L., Gosling, J., Cleary, M., Charo, I. F. Decreased lesion formation in CCR2–/– mice reveals a role for chemokines in the initiation of atherosclerosis. Nature. 1998, 394:894–897.
86.Boisvert, W. A., Santiago, R., Curtiss, L. K. Terkeltaub, R. A. A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest. 1998, 101:353–363.
87.Clinton, S., Underwood, R., Sherman, M., Kufe, D., Libby, P. Macrophage-colony stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol. 1992, 140:301–316.
88.Rosenfeld, M. Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans. Am J Pathol. 1992, 140:291–300.
89.Sugiyama, S. Macrophage myeloperoxidase regulation by granulocyte macrophage colonystimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol. 2001, 158:879–891.
90.Davies, M. J. Stability and instability: the two faces of coronary atherosclerosis. The Paul Dudley White Lecture, 1995. Circulation. 1996, 94:2013–2020.
91.Virmani, R., Burke, A. P., Farb, A., Kolodgie, F. D. Pathology of the unstable plaque. Prog Cardiovasc Dis. 2002, 44:349–356.
92.Rajavashisth, T. B. Inflammatory cytokines and oxidized low density lipoproteins increase endothelial cell expression of membrane type 1-matrix metalloproteinase. J Biol Chem. 1999, 274:11924–11929.
93.Faggiotto, A., Ross, R., Harker, L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis. 1984, 4:323–340.
94.de Boer, O. J., van der Wal, A. C., Teeling, P., Becker, A. E. Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization? Cardiovasc Res. 1999, 41:443–449.
95.Brogi, E. Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and non-atherosclerotic arteries: association of acidic FGF with plaque microvessels and macrophages. J Clin Invest. 1993, 92:2408–2418.
96.Ramos, M. A. Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions. Arterioscler.Thromb Vasc Biol. 1998, 18:1188–1196.
97.Moulton, K. S. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation. 1999, 99:1726–1732.
98.Libby, P. The molecular bases of the acute coronary syndromes. Circulation. 1995, 91:2844–2850.
99.Lee, R. and Libby, P. The unstable atheroma. Arterioscler Thromb Vasc Biol. 1997, 17:1859–1867.
100.Galis, Z., Sukhova, G., Lark, M., Libby, P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994, 94:2493–2503.
101.Sukhova, G. K. Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation. 1999, 99:2503–2509.

102.Herman, M. P. Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling. Circulation. 2001, 104:1899–1904.
103.Saren, P., Welgus, H. G., Kovanen, P. T. TNF-a and IL-1b selectively induce expression of 92-kDa gelatinase by human macrophages. J Immunol. 1996, 157:4159–4165.
104.Kovanen, P. T., Kaartinen, M., Paavonen, T. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. Circulation. 1995, 92:1084–1088.
105.Brand, K., G. Rogler, A. Bartsch, R. Knuechel, M. Page, C. Kaltschmidt, Baeuerle, P. A., Neumeier, D. Transcription factor NF-kB/Rel is activated in the atherosclerotic lesion. J Clin Invest. 1996, 97: 1715-1722.
106.Sen, R. and Baltimore, D. lnducibility of κ lmmunoglobulin Enhancer-Binding Protein NF-κB by a Posttranslational Mechanism. Cell. 1966, 47:921-926.
107.Moynagh, P. N. The NF-kB pathway. J cell sci. 2005, 118:4589-4592.
108.Ghosh, S., May, M. J., Kopp, E. B. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998, 16:225-260.
109.Silverman, N. and Maniatis, T. NF-kB signaling pathways in mammalian and insect innate immunity. Genes Dev. 2001, 15: 2321–2342
110.Ghosh, S. and Karin, M. Missing pieces in the NF-kB puzzle. Cell. 2002, 109:S81–S96
111.Yamamoto, Y. and Gaynor, R. B. IkB kinases: key regulators of the NF-kB pathway. TRENDS in biochemical sciences. 2004, 29:72-79
112.Patrick, A., Baeuerle, U., Baltimore, D. NF-kB: ten years after. Cell. 1996, 87:13-20
113.Urban, M. B., Schreck, R., Baeuerle, P. A. NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit. EMBO J. 1991, 10:1817–1825.

114.Baeuerle, P. A. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits. Biochim Biophys Acta. 1991, 1071:63-80
115.Collins, T. Endothelial nuclear factor-KB and the initiation of the atherosclerotic lesion. Lab Invest. 1993, 68:499-508
116.Brand, K., Page, S., Rogler, G. Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest. 1996, 97:1715-1722
117.Berliner, J., Navab, M., Fogelman, A. Atherosclerosis : basic mechanisms : Oxidation, inflammation and genetics. Circulation. 1995, 1:2489-96
118.Liao, F., Andalibi, A. L., Qiao, J. H. Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice. J Clin Invest. 1994, 94:877-84
119.Nakajima, T., Kitajimaf, L., Shin, H. Involvement of NF-κB activation in thrombin-induced hum an vascular smooth muscle cells. Biochent Biophys Res C onrnr. 1994, 104:95 0-55
120.Kranzhofe, R., Schmiclt, J., Pfeiffer, C. A. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vase Biol. 1999, 19:1613-9
121.Han, Y., Runge, M. S., Brasier, A. R. Angiotensin induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-kappa B transcription factors. Ore Res. 1999, 84:695-703
122.Kranzhofer, R., Browatzki, M., Schmidt, J.. Angiotensin activates the proinflanunatory transcription factor nuclear factor-kappa B in human monocytes. Biochem Biophys Res Commun. 1999, 157:816-8
123.Ross, R. The pathogenesis of atherosclerosis : a perspective for the 1990s. Nature. 1993, 362:801-809
124.Barath, P., Fishbein, M. C., Lao, J. Tumor necrosis factor gene expression in human vascular smooth muscle cells detected by in vitro hybridization. Am J Pathol. 1990, 137:503-509
125.Hiscott, J., Marais, J., Garoufalis, J. Characterization of a functional NF-kappa B site in the human interleukin-lβ promoter : evidence for a positive autoregulatory loop. Mol Cell Biol. 1993, 13:6231- 6140
126.Terkeltaccb, R., Banks, C. L., Solon, J. Oxidized LDL induces monocytic cell expression of interleukin-8, acheinkine with T-lymphocyte chemotactic activity. Arterioscler Throntb. 1994, 14:47-53
127.Cushing, S. D., Berliner, J. A., Valente, A. J. Minimally modified LDL Induces monocyte chemotactic protein-I in human endothelial and smooth muscle cells. Proc Nail Acad Sci USA. 1990, 87:5134-5138
128.Drake, T., Hannani, K., Fei, H. Minimally oxidized low-density lipoprotein induces tissue factor expression incultured human endothelial cells. Am J Pathol. 1991, 138:601-607
129.Duyao, M. P., Buckler, A. J., Sonenshein, G. E. Interaction of an NF-kappa B like factor with a site upstream of the c-myc promoter. Proc Natl Acad Sci USA. 1990, 87:4717-4731
130.Rodriguez, M., Michalopoulos, I., Arenzana-Seisdedos, F. Inducible degradation of IκB. in vitro and in vivo requires the acidic C-terminal domain of the protein. Mol Cell Bio. 1995, 15:2413-19
131.Alan, D. Mouse models of atherosclerosis. Am J Med Sci. 2002, 323:3-10
132.Shore, B., Shone, V. G. Heterogeneity of human plasma very low density lipoproteins: separations of species in protein components. Biochemistry. 1973, 12:502-510.
133.Raii, S. C., Weisgraber, K. H.,Mahley, R. W..Human apolipoprotein E:th e complete amino acid sequence. J Biol Chem. 1982, 257:4171-4179.
134.山田信博.ヤдE蛋白ソ構造シ脂質代謝ズやんペ. 醫學ソやバノ. 1995, 174:579-592.
135.石川俊次.血漿質,эд蛋白ソ基礎知識. 治療. 1988, 70:1-12 .
136.Brown, M. S., Goldstein, J. L. A receptor-mediated pathway for chorleste rol homeostasis.Science. 1986, 232:34-42.

137.Reddick, R. L, Zhang, S. H., Maeda, N. Atherosclerosis in mice lacking apo E evalution of lesional development and progression. Arteriosc ler Thromb. 1994, 14:141-147.
138.Jaffe, E. A., Nachman, R. L., Becker, C. G., Minick, R. C. Culture of human endothelium cells derived from umbilical veins: identification by morphologic and immunologic criteria. J Clin Invest. 1973, 52: 2745-2756.
139.Sambroock, J., Fritsch E. F., Maniatis, T. Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. 1989
140.Breslow, J. L. Mouse models of atherosclerosis. Science. 1996, 272: 685-688.
141.Reddick, R. L., Zhang, S. H., Maeda, N.. Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression. Arterioscler Thromb. 1994, 14:839-847.
142.Smithies, O. and Maeda, N. Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension. Proceedings of the National Academy of Sciences of the United States of America. 1995, 92:5266-5272.
143.Falk, E., Shah, P. K., Fuster, V. Coronary plaque disruption. Circulation. 1995, 92:657-671.
144.Kim, I., Moon, S. O., Kim, S. H., Kim, H. J., Koh, Y. S., Koh, G. Y.. Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and E-selectin through Nuclear Factor-kB Activation in Endothelial Cells. J Biol Chem. 2001, 276:7614–7620
145.Gimbrone, M. A. In Molecular Cardiovascular Medicine. (Haber, E., ed) Scientific American Medicine, New York. 1995, 49-61
146.Gimbrone, M. A., Nagel, T., Topper, J. N. Biomechanical activation: an emerging paradigm in endothelial adhesion biology. J Clin Invest. 1997, 100:S61–S65

147.Bischoff, J. Cell adhesion and angiogenesis. J Clin Invest. 1997, 100: S37–S39
148.Price, D. T., Loscalzo, J. Cellular adhesion molecules and atherogenesis. Am J Med. 1999, 107:85–97
149.Cybulsky, M. I., Gimbrone, J. R. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991, 251: 788–791.
150.Collins, T., Read, M. A., Neish, A. S. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995, 9:899–909.
151.Lenardo, M, J., Baltimore, D. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989, 58:227–229.
152.Baeuerle, P. A., Henkel, T. Function and activation of NF-kB in the immune system. Annu Rev Immunol. 1994, 12:141–179.
153.Thanos, D., Maniatis, T. NF-kB: a lesson in family values. Cell. 1995, 80: 529–532.
154.Fuchs, J., Zollner, T. M., Kaufmann, R. Redox-modulated pathways in inflammatory skin diseases. Free Radicals Biol Med. 2001, 30:337–353.
155.Weber, C., Erl, W., Pietsch, A. Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kB mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals. Arterioscler Thromb. 1994, 14:1665–1673.
156.Khan, B. V., Harrison, D. G., Olbrych, M. T. Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci USA. 1996, 93:9114–9119.
157.Rahman, A., Kefer, J., Bando, M. E-selectin expression in human endothelial cells by TNF-a induced oxidant generation and NF-kB activation. Am J Physiol. 1998, 275:L533–L544.

158.Ding, M., Zhao, G. R., Yuan, Y. J., Guo, Z. X. Aqueous Extract of Salvia miltiorrhoza Regulates Adhesion Molecule Expression of Tumor Necrosis Factor a–Induced Endothelial Cells by Blocking Activation of Nuclear Factor kB. J Cardiovasc Pharmacol. 2005, 45:516-524.
159.Schonbeck, U., Sukhova, G.K., Graber, P., Coulter, S., Libby, P. Augmented expression of cyclooxygenase-2 in human atherosclerotic lesions. Am J Pathol. 1999, 155:1281– 1291.
160.Baker, C. S., Hall, R. J., Evans, T. J., Pomerance, A., Maclouf, J., Creminon, C., Yacoub, M. H., Polak, J. M. Cyclooxygenase- 2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizeswith inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arterioscler Thromb Vasc Biol. 1999, 19:646–655.
161.Belton, O., Byrne, D., Kearney, D., Leahy, A., Fitzgerald, D.J. Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis. Circulation. 2000, 102:840– 845.
162.Cipollone, F., Prontera, C., Pini, B., Marini, M., Fazia, M., De Cesare, D., Iezzi, A., Ucchino, S., Boccoli, G., Saba, V., Chiarelli, F., Cuccurullo, F., Mezzetti, A. Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation. 2001, 104:921–927.
163.Williams, C. S. The role of cyclooxygenases in inflammation,cancer, and development. Oncogene. 1999, 18:7908–7916.
164.Smith, W. L. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000, 69:145–182.
165.Appleby, S. B., Ristmaki, A., Neilson, K., Narko, K., Hla, T. Structure of the human cyclo-oxygenase-2 gene. Biochem J. 1994, 302:723-727
166.Chen, C. C., Sun, Y. T., Chen, J. J., Chiu, K. T. TNF-a-induced cyclooxygenase-2 expression in human lung epithelial cells: involvement of the phospholipase C-γ2, protein kinase C-α, tyrosine kinase, NF-κB-inducing kinase, and InB Kinase 1/2 pathway, J. Immunol. 2000, 165:2719–2728.
167.Lukiw, W., Bazan, N. Strong nuclear factor-kappaB-DNA binding parallels cyclooxygenase-2 gene transcription in aging and sporadic Alzheimer’s disease superior temporal lobe neocortex. J Neurosci Res. 1998, 53:583– 592.
168.Morisaki, N., Kanzaki, T., Tamura, K. Specific inhibition of vascular cell adhesion molecule-1 expression by type IV collagen in endothelial cells. Biochem Biophys Res Commun. 1995, 214:1163-7
169.Linton, M. F. and Fazio, S. Macrophages, inflammation, and atherosclerosis. Int J Obes Relat Metab Disord. 2003, 27:35–40
170.Rosenfeld, M. E. Leukocyte recruitment into developing atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2002, 22:361–363
171.Aikawa, M. and Libby, P. Atherosclerotic plaque inflammation: the final frontier? Can J Cardiol. 2004, 20:631–634
172.Steffens, S., and Mach, F. Inflammation and atherosclerosis. Herz, 2004, 29:741–748
173.Libby, P. and Hansson, G. K. Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. Lab Invest. 1991, 64:5–15.
174.Hatada, E. N., Krappmann, D., Scheidereit, C. NF-κB and the innate immune response. Curr Opin Immunol. 2000, 12:52–58
175.Barnes, P. J. and Karin, M. Nuclear Factor-κB a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997, 336:1066–1071
176.Lim, S., Kang,K. W., Park, S. Y., Kim, S. I., Choi, Y. S., Kim, N. D., Lee, K. U., Lee, H. K., Pak, Y. K. Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase expression by a novel compound, mercaptopyrazine, through suppression of nuclear factor-kappaB binding to DNA. Biochem Pharm. 2004, 68:719–728

177.Michel, T. and Feron, O. Nitric oxide synthases: which, where, how, and why? J Clin Invest. 1997, 100:2146–2152.
178.Mayer, B., Hemmens, B. Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem Sci. 1997, 22:477–481.
179.Brown, G. C. Cell biology. NO says yes to mitochondria. Science. 2003, 299:838–839.
180.Xie, Q. W., Whisnant, R., Nathan, C. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide. J Exp Med. 1993, 177:1779–1784.
181.Kim, Y. M., Lee, B. S.,Yi, K. Y., Paik, S. G.. Upstream NF-kappaBsite is required for the maximal expression of mouse inducible nitric oxide synthase gene in interferon-gamma plus lipopolysaccharide-induced RAW 264.7 macrophages. Biochem Biophys Res Commun. 1997, 236:655–660.
182.Ferraccioli, G. and Gremese, E. Related Articles, Links • Abstract, Thrombogenicity of TNF alpha in rheumatoid arthritis defined through biological probes: TNF alpha blockers. Autoimmun. Rev. 2004, 3:261–266
183.Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C., Chrousos, G. P. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998, 128:127–137
184.Sukovich, D. A., Kauser, K., Shirley, F. D., DelVecchio, V., Halks-Miller, M., Rubanyi, G. M. Expression of interleukin-6 in atherosclerotic lesions of. male ApoE-knockout mice: inhibition by 17beta-estradiol. Arterioscler Thromb Vasc Biol. 1998, 18:1498–1505
185.Tipping, P. G. and Hancock, W. W. Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques. Am J Pathol. 1993, 142:1721–1728
186.Rajavashisth, T. B., Xu, X. P., Jovinge, S., Meisel, S., Xu, X. O., Chai, N. N., Fishbein, M. C., Kaul, S., Cercek, B., Sharifi, B., Shah, P. K. Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques - Evidence for activation by proinflammatory mediators. Circulation. 1999, 99:3103–3109
187.Schleef, R. R., Bevilacqua, M. P., Sawdey, M., Gimbrone, M. A., Jr., Loskutoff, D. J. Cytokine-activation of vascular endothelium: effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J Biol Chem. 1988, 263:5797–5803
188.Kelk, P., Claesson, R., Hanstrom, L., Lerner, U. H., Kalfas, S., Johansson, A. Abundant Secretion of Bioactive Interleukin-1{beta} by Human Macrophages Induced by Actinobacillus actinomycetemcomitans Leukotoxin. Infect Immun. 2005, 73:453–458
189.Moyer, C. F., Sajuthi, D., Tulli, H., Williams, J. K. Synthesis of IL-1 alpha and IL-1 beta by arterial cells in atherosclerosis. Am J Pathol. 1991, 138:951–960
190.Lane, A., Graham, L., Cook, M., Chantry, D., Green, F., Nigon, F., Humphries, S. E. Cytokine production by cholesterol-loaded human peripheral monocyte-macrophages: the effect on fibrinogen mRNA levels in a hepatoma cell-line (HepG2). Biochim Biophys Acta. 1991, 1097:161–165
191.Ku, G.., Thomas, C. E., Akeson, A. L., Jackson, R. L. Induction of interleukin 1 beta expression from human peripheral blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid. J Biol Chem. 1992, 267:14183–14188
192.Fong, L. G., Fong, T. A., Cooper, A. D. Inhibition of lipopolysaccharide-induced interleukin-1 beta mRNA expression in mouse macrophages by oxidized low density lipoprotein . J Lipid Res. 1991, 32: 1899–1910
193.Harrison, L. M., van den Hoogen, C., van Haaften, W. C., Tesh, V. L. Chemokine Expression in the Monocytic Cell Line THP-1 in Response to Purified Shiga Toxin 1 and/or Lipopolysaccharides. Infect. Immun. 2005, 73:403–412
194.Auron, P. E. and Webb, A. C. Interleukin 1: A gene expression system regulated at multiple levels. Eur Cytokine Netw. 1994:573–592
195.Muegge, K. and Durum, S. K. Cytokines and transcription factors. Cytokine. 1990, 2:1–8
196.Dinarello, C. A. Interleukin-1 and interleukin-1 antagonism. Blood. 1991, 77:1627–1652
197.Dinarello, C. A. Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int. Rev. Immunol. 1998. 16:457–499
198.Netea, M. G., Hancu, N., Blok, W. L., Grigorescu-Sido, P., Popa, L., Popa, V., and van der Meer, J. W. Interleukin 1 beta, tumour necrosis factor-alpha and interleukin 1 receptor antagonist in newly diagnosed insulin-dependent diabetes mellitus: comparison to long-standing diabetes and healthy individuals. Cytokine. 1997, 9:284–287
199.Rosselet, A., Feihl, F., Markert, M.,Gnaegi, A., Perret, C., Liaudet, L. Selective iNOS inhibition is superior to norepinephrine in the treatment of rat endotoxic shock. Am J Respir Crit Care Med. 1998, 157:162–70.
200.Cho, S., Kim, Y., Cruz, M. O., Park, E. M., Chu, C. K., Song, G. Y. Repression of proinflammatory cytokine and inducible nitric oxide synthase (NOS2) gene expression in activated microglia by N-acetyl- O-methyldopamine: protein kinase A-dependent mechanism. Glia. 2001, 33:324–33.
201.Dannenberg, A. J., Altorki, N. K., Boyle, J. O. Cyclooxygenase-2: A pharmacological target for the prevention of cancer. Lancet Oncol. 2001, 2:544-511
202.Williams, C. S. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 1999, 18:7908–7916.
203.Burleigh, M. E., Babaev, V. R., Oates, J. A. Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor-deficient mice. Circulation. 2002, 105:1816–1823.
204.Bourcier, T., Sukhova, G., Libby, P. The nuclear factor kB signaling pathway participates in dysregulation of vascular smooth muscle cells in vitro and in human atherosclerosis. J Biol Chem. 1997, 272:15817–15824.

205.Siebenlist, U., Franzoso, G., Brown, K. Structure, regulation, and function of NF-kB. Annu Rev Cell Biol. 1994, 10:405– 455.
206.Lawrence, R., Chang, L. J., Siebenlist, U., Bressler, P., Sonenshien, G. E. Vascular smooth muscle cells express a constitutive NF-kB like activity. J Biol Chem. 1994, 269:28913–28918.
207.Baldwin AS. The NF-kB, and IkB proteins: new discoveries and insights. Annu Rev Immunol. 1996, 14:649–681.
208.Han D. K., Haudenschild C. C., Hong M. K. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model.Am J Pathol. 1995, 147:267-77.
209.Ross R, Raines E. W., Bowen-pope D. E. The biology of platelet derived growth factor. Cell. 1986, 46:155-169.
210.Ferns G. A. A., Raines E. W., Sprugel K. H., Motani A. S., Reidy M. A., Ross R. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science. 1991, 253:1129-1132.
211.Cucina, S. Pagliei, V. Borrelli, V. Corvino, F. Stipa, A. Cavallaro and A. V. Sterpetti. Oxidised LDL (OxLDL) Induces Production of Platelet Derived Growth Factor AA (PDGF AA) From Aortic Smooth Muscle Cells. Eur J Vasc Endovasc Surg. 1998, 16:197-202.
212.Zoltan Kaposzta, John F, Martin F. Switching off embolization from symptomatic carotid plaque using s-nitrosoglutathione. Circulation. 2002, 99:1480-1484.
213.Dannenberg A. J., Altorki N. K., Boyle J. O. Cyclooxygenase-2. Oncol. 2001, 2:544-511
214.Morita I, Schindler M, Regier M. K. Different intracellular locations for prostaglandin endoperoxide H synthase-1 and-2. J Bio Chem. 1995, 270:10902-10908
215.Burleigh ME, Babaev VR, Oates JA, et al. Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor-deficient mice. Circulation. 2002, 105:1816–1823.
216.Pratico D, Tillmann C, Zhang Z. B. Accelera-tion of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice. Proc Natl Acad Sci USA. 2001, 98:3358–3363.
217.Krul E. S, Napawan N, Butteiger D. T. Atherosclerosis is reduced in cholesterol-fed ApoE(-/-) mice administered an ASBT inhibitor or a selective COX-2 inhibitor. Arterioscler Thromb Vasc Biol. 2002, 22:409.
第一頁 上一頁 下一頁 最後一頁 top