跳到主要內容

臺灣博碩士論文加值系統

(18.97.9.173) 您好!臺灣時間:2024/12/02 00:59
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:姚博軒
研究生(外文):YAO, BO-SYUAN
論文名稱:LOX-1 調控 L5-LDL 在細胞內的轉運且誘發粒線體功能失調和內皮細胞凋亡
論文名稱(外文):LOX-1-mediated intracellular trafficking of L5-LDL induces mitochondrial dysfunction and endothelial apoptosis
指導教授:柯良胤
指導教授(外文):KE, LIANG-YIN
口試委員:沈國屏梁世欣
口試委員(外文):SHEN, KUO-PINGLIANG, SHIH-SHIN
口試日期:2022-01-11
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:醫學研究所碩士班
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2022
畢業學年度:110
語文別:中文
論文頁數:87
中文關鍵詞:L5-LDL
外文關鍵詞:L5-LDL
相關次數:
  • 被引用被引用:0
  • 點閱點閱:84
  • 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:0
縮寫 (Abbreviation)..................................1
中文摘要 (Abstract)..................................4
英文摘要 (Abstract)..................................7
致謝 (Acknowledgements)..............................10
第一章:緣起 (Introduction)...........................13
一、 心血管疾病在全球的發展與治療方針...................14
二、 膽固醇在動脈粥樣硬化心血管疾病的影響...............15
三、 致病性脂蛋白的作用...............................17
四、 陰電性脂蛋白相關研究.............................18
五、 SOD2與CAV-1作為壓力適應的調控器保護粒線體.........20
六、 陰電性脂蛋白導致粒線體裂變及內皮細胞凋亡...........23
第二章:研究目的 (Purpose)............................25
第三章:材料與方法 (Materials and Methods)............27
一、 低密度脂蛋白分離................................28
二、 細胞培養........................................29
三、 蛋白質定量......................................29
四、 蛋白質萃取......................................30
五、 氧化低密度脂蛋白.................................30
六、 陰電性脂蛋白:L1及L5純化分離......................30
七、 脂質染色........................................32
八、 細胞染色........................................32
九、 粒線體分離......................................33
十、 穿透式電子顯微鏡.................................34
十一、 西方墨點法.....................................34
十二、 消化水解.......................................37
十三、 細胞凋亡實驗...................................38
第四章:結果 (Results)................................40
一、 PCSK9 Inhibitors無法明顯降低病人血漿L5-LDL濃度....41
二、 L5-LDL在細胞內被運送至粒線體......................41
三、 L5-LDL對粒線體型態與功能的影響....................42
四、 L5-LDL影響粒腺體的蛋白質表現量....................43
五、 L5-LDL導致血管內皮細胞凋亡.......................43
第五章:討論 (Discussion).............................45
本研究主要發現.......................................46
臨床意義 ............................................46
研究限制.............................................48
第六章:結論 (Conclusion).............................50
參考文獻 (References)................................52
圖 (Figures)........................................59

1. Beevers, D.G., The atlas of heart disease and stroke. Journal of Human Hypertension, 2005. 19(6): p. 505-505.
2. Roth, G.A., et al., Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019. 2020. 76(25): p. 2982-3021.
3. Day, I.S.C.f.W.T., Thrombosis: a major contributor to the global disease burden. J Thromb Haemost, 2014. 12(10): p. 1580-1590.
4. Francula-Zaninovic, S. and I.A. Nola, Management of Measurable Variable Cardiovascular Disease' Risk Factors. Curr Cardiol Rev, 2018. 14(3): p. 153-163.
5. Masana, L., et al., Is there a role for lifestyle changes in cardiovascular prevention? What, when and how? Atheroscler Suppl, 2017. 26: p. 2-15.
6. Casas, R., et al., Nutrition and Cardiovascular Health. Int J Mol Sci, 2018. 19(12):3988.
7. Yusuf, S., et al., Global Burden of Cardiovascular Diseases. 2001. 104(22): p. 2746-2753.
8. Stamler, J., et al., Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women. Jama, 1999. 282(21): p. 2012-2018.
9. Sabatine, M.S., et al., Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med, 2017. 376(18): p. 1713-1722.
10. Baigent, C., et al., Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet, 2010. 376(9753): p. 1670-1681.
11. Arnett, D.K., et al., 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 2019. 140(11): p. e563-e595.
12. Abifadel, M., et al., Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet, 2003. 34(2): p. 154-156.
13. Rashid, S., et al., Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A, 2005. 102(15): p. 5374-5379.
14. Reiner, Z., Resistance and intolerance to statins. Nutr Metab Cardiovasc Dis, 2014. 24(10): p. 1057-1066.
15. Packard, C., et al., Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges. Heart, 2021. 107(17): p. 1369-1375.
16. Yadav, K., M. Sharma, and K.C. Ferdinand, Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: Present perspectives and future horizons. Nutr Metab Cardiovasc Dis, 2016. 26(10): p. 853-862.
17. Lambert, G., et al., The PCSK9 decade. J Lipid Res, 2012. 53(12): p. 2515-2524.
18. Page, M.M. and G.F. Watts, PCSK9 inhibitors - mechanisms of action. Aust Prescr, 2016. 39(5): p. 164-167.
19. Alexander, R.W., Hypertension and the Pathogenesis of Atherosclerosis. 1995. 25(2): p. 155-161.
20. Gidding, S.S. and N.B. Allen, Cholesterol and Atherosclerotic Cardiovascular Disease: A Lifelong Problem. 2019. 8(11): p. e012924.
21. Henning, R.J., Obesity and obesity-induced inflammatory disease contribute to atherosclerosis: a review of the pathophysiology and treatment of obesity. Am J Cardiovasc Dis, 2021. 11(4): p. 504-529.
22. Stary, H.C., et al., A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of Atherosclerosis. 1995. 92(5): p. 1355-1374.
23. Sanz, J. and Z.A. Fayad, Imaging of atherosclerotic cardiovascular disease. Nature, 2008. 451(7181): p. 953-957.
24. Moriya, J., Critical roles of inflammation in atherosclerosis. J Cardiol, 2019. 73(1): p. 22-27.
25. Libby, P., Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol, 2012. 32(9): p. 2045-2051.
26. Mayerl, C., et al., Atherosclerosis research from past to present--on the track of two pathologists with opposing views, Carl von Rokitansky and Rudolf Virchow. Virchows Arch, 2006. 449(1): p. 96-103.
27. Risk Factors in Coronary Heart Disease. 1964. 61(5_Part_1): p. 888-899.
28. Libby, P., et al., Atherosclerosis. Nat Rev Dis Primers, 2019. 5(1): p. 56.
29. Ravnskov, U., Is atherosclerosis caused by high cholesterol? QJM: An International Journal of Medicine, 2002. 95(6): p. 397-403.
30. Carmena, R., P. Duriez, and J.C. Fruchart, Atherogenic lipoprotein particles in atherosclerosis. Circulation, 2004. 109(23 Suppl 1): p. III2-7.
31. Boren, J., et al., Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J, 2020. 41(24): p. 2313-2330.
32. Havel, R.J., H.A. Eder, and J.H. Bragdon, The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest, 1955. 34(9): p. 1345-1353.
33. Gofman, J.W., F.T. Lindgren, and H. Elliott, Ultracentrifugal studies of lipoproteins of human serum. J Biol Chem, 1949. 179(2): p. 973-979.
34. Miller, Y.I., et al., Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ Res, 2011. 108(2): p. 235-248.
35. Navab, M., et al., The oxidation hypothesis of atherogenesis: the role of oxidized phospholipids and HDL. J Lipid Res, 2004. 45(6): p. 993-1007.
36. Kuzuya, M., et al., Role of lipoprotein-copper complex in copper catalyzed-peroxidation of low-density lipoprotein. Biochim Biophys Acta, 1992. 1123(3): p. 334-341.
37. Itabe, H., T. Obama, and R. Kato, The Dynamics of Oxidized LDL during Atherogenesis. J Lipids, 2011. 2011: p. 418313.
38. Sawamura, T., et al., An endothelial receptor for oxidized low-density lipoprotein. Nature, 1997. 386(6620): p. 73-77.
39. Salvayre, R., et al., Oxidized low-density lipoprotein-induced apoptosis. Biochim Biophys Acta, 2002. 1585(2-3): p. 213-221.
40. Chen, C.H., et al., Low-density lipoprotein in hypercholesterolemic human plasma induces vascular endothelial cell apoptosis by inhibiting fibroblast growth factor 2 transcription. Circulation, 2003. 107(16): p. 2102-2108.
41. Yang, C.Y., et al., Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins. Arterioscler Thromb Vasc Biol, 2003. 23(6): p. 1083-1090.
42. Avogaro, P., G.B. Bon, and G. Cazzolato, Presence of a modified low density lipoprotein in humans. 1988. 8(1): p. 79-87.
43. Demuth, K., et al., A Cytotoxic Electronegative LDL Subfraction Is Present in Human Plasma. 1996. 16(6): p. 773-783.
44. Estruch, M., et al., Electronegative LDL: a circulating modified LDL with a role in inflammation. Mediators Inflamm, 2013. 2013: p. 181324.
45. Tang, D., et al., Electronegative LDL circulating in smokers impairs endothelial progenitor cell differentiation by inhibiting Akt phosphorylation via LOX-1. J Lipid Res, 2008. 49(1): p. 33-47.
46. Chang, P.Y., et al., Aspirin protects human coronary artery endothelial cells against atherogenic electronegative LDL via an epigenetic mechanism: a novel cytoprotective role of aspirin in acute myocardial infarction. Cardiovasc Res, 2013. 99(1): p. 137-145.
47. Wang, G.-J., et al., Negatively charged L5 as a naturally occurring atherogenic low-density lipoprotein. BioMedicine, 2012. 2(4): p. 147-154.
48. Chan, H.C., et al., Highly electronegative LDL from patients with ST-elevation myocardial infarction triggers platelet activation and aggregation. Blood, 2013. 122(22): p. 3632-3641.
49. Chang, C.T., et al., Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis. Medicine (Baltimore), 2016. 95(2): p. e2265.
50. Hsu, J.F., et al., Low-density lipoprotein electronegativity is a novel cardiometabolic risk factor. PLoS One, 2014. 9(9): p. e107340.
51. Chu, C.S., et al., Range of L5 LDL levels in healthy adults and L5's predictive power in patients with hyperlipidemia or coronary artery disease. Sci Rep, 2018. 8(1): p. 11866.
52. Chu, C.S., et al., Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis. Biomedicines, 2020. 8(8):254.
53. Lu, J., et al., Electronegative LDL impairs vascular endothelial cell integrity in diabetes by disrupting fibroblast growth factor 2 (FGF2) autoregulation. Diabetes, 2008. 57(1): p. 158-166.
54. Wang, Y.C., et al., Human electronegative LDL induces mitochondrial dysfunction and premature senescence of vascular cells in vivo. Aging Cell, 2018. 17(4): p. e12792.
55. Chen, W.Y., et al., Role of apolipoprotein E in electronegative low-density lipoprotein-induced mitochondrial dysfunction in cardiomyocytes. Metabolism, 2020. 107: p. 154227.
56. Antico Arciuch, V.G., et al., Mitochondrial regulation of cell cycle and proliferation. Antioxid Redox Signal, 2012. 16(10): p. 1150-1180.
57. Anderson, A.J., et al., Mitochondria—hubs for regulating cellular biochemistry: emerging concepts and networks. 2019. 9(8): p. 190126.
58. Osellame, L.D., T.S. Blacker, and M.R. Duchen, Cellular and molecular mechanisms of mitochondrial function. Best Pract Res Clin Endocrinol Metab, 2012. 26(6): p. 711-723.
59. Sagan, L., On the origin of mitosing cells. J Theor Biol, 1967. 14(3): p. 255-274.
60. Kuhlbrandt, W., Structure and function of mitochondrial membrane protein complexes. BMC Biol, 2015. 13: p. 89.
61. Cogliati, S., J.A. Enriquez, and L. Scorrano, Mitochondrial Cristae: Where Beauty Meets Functionality. Trends Biochem Sci, 2016. 41(3): p. 261-273.
62. Anderson, S., et al., Sequence and organization of the human mitochondrial genome. Nature, 1981. 290(5806): p. 457-465.
63. Needs, H.I., et al., Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration. Life (Basel), 2021. 11 ;11(5):432.
64. Bause, A.S. and M.C. Haigis, SIRT3 regulation of mitochondrial oxidative stress. Exp Gerontol, 2013. 48(7): p. 634-639.
65. He, J., et al., Inhibition of Mitochondrial Oxidative Damage Improves Reendothelialization Capacity of Endothelial Progenitor Cells via SIRT3 (Sirtuin 3)-Enhanced SOD2 (Superoxide Dismutase 2) Deacetylation in Hypertension. Arterioscler Thromb Vasc Biol, 2019. 39(8): p. 1682-1698.
66. Chen, M.L., et al., Trimethylamine-N-Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3-SOD2-mtROS Signaling Pathway. J Am Heart Assoc, 2017. 6(9) :e006347.
67. Dikalova, A.E., et al., Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress. Circ Res, 2020. 126(4): p. 439-452.
68. Dikalova, A.E., et al., Sirt3 Impairment and SOD2 Hyperacetylation in Vascular Oxidative Stress and Hypertension. Circ Res, 2017. 121(5): p. 564-574.
69. Mastrodonato, M., et al., Altered distribution of caveolin-1 in early liver steatosis. Eur J Clin Invest, 2011. 41(6): p. 642-651.
70. Fridolfsson, H.N., et al., Regulation of intracellular signaling and function by caveolin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. 28(9): p. 3823-3831.
71. Fridolfsson, H.N., et al., Mitochondria-localized caveolin in adaptation to cellular stress and injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. 26(11): p. 4637-4649.
72. Schilling, J.M., B.P. Head, and H.H. Patel, Caveolins as Regulators of Stress Adaptation. Mol Pharmacol, 2018. 93(4): p. 277-285.
73. Sun, S.W., et al., Caveolae and caveolin-1 mediate endocytosis and transcytosis of oxidized low density lipoprotein in endothelial cells. Acta Pharmacol Sin, 2010. 31(10): p. 1336-1342.
74. Matarazzo, S., et al., Cholesterol-lowering drugs inhibit lectin-like oxidized low-density lipoprotein-1 receptor function by membrane raft disruption. Mol Pharmacol, 2012. 82(2): p. 246-254.
75. Ramirez, C.M., et al., Caveolin-1 Regulates Atherogenesis by Attenuating Low-Density Lipoprotein Transcytosis and Vascular Inflammation Independently of Endothelial Nitric Oxide Synthase Activation. Circulation, 2019. 140(3): p. 225-239.
76. Youle, R.J. and M. Karbowski, Mitochondrial fission in apoptosis. Nature Reviews Molecular Cell Biology, 2005. 6(8): p. 657-663.
77. Lu, J., et al., Mediation of Electronegative Low-Density Lipoprotein Signaling by LOX-1. 2009. 104(5): p. 619-627.
78. Bhatti, J.S., G.K. Bhatti, and P.H. Reddy, Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis, 2017. 1863(5): p. 1066-1077.
79. Scott, I. and R.J. Youle, Mitochondrial fission and fusion. Essays Biochem, 2010. 47: p. 85-98.
80. Raskob, G.E., et al., Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol, 2014. 34(11): p. 2363-2371.
81. Shapiro, M.D., H. Tavori, and S. Fazio, PCSK9: From Basic Science Discoveries to Clinical Trials. Circ Res, 2018. 122(10): p. 1420-1438.
82. Ding, Z., et al., Cross-talk between LOX-1 and PCSK9 in vascular tissues. Cardiovasc Res, 2015. 107(4): p. 556-567.
83. Zhang, X., et al., Cav-1 (Caveolin-1) Deficiency Increases Autophagy in the Endothelium and Attenuates Vascular Inflammation and Atherosclerosis. Arterioscler Thromb Vasc Biol, 2020. 40(6): p. 1510-1522.

電子全文 電子全文(網際網路公開日期:20270117)
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
1. 孝為先下的長照:護理之家家屬孝道信念、善終觀念與其安寧療護選擇之相關性研究
2. 運用外傷登錄資料庫探討創傷性骨盆骨折檢查與手術對預後之影響
3. 自我修養的幸福學:「心安理得」之概念分析及其量表編製
4. 父不慈,子還要孝嗎?父母違反角色義務對要求盡孝權利與子女孝順義務之影響:雙元孝道之調節效果
5. 失智症危險因子和相關致病機轉探討: 聚焦在血糖變化和神經發炎以及 藥物使用和睡眠結構改變
6. 人越多越想買?排隊人數對消費意願之影響: 以產品價值與排隊厭惡為中介
7. 以系統性文獻回顧探討鼻敷料相關照護以減少早產兒鼻導管持續性正壓呼吸器(NCPAP)治療所造成之鼻損傷
8. 老鼠在產前嗎啡暴露下腦區分子結構的中長期變化和發炎及其表觀基因表現及治療策略研發
9. 台灣南部醫院人類免疫缺乏病毒與C型肝炎共同感染者之C型肝炎分子流行病學
10. 異體造血幹細胞移植術後巨細胞病毒感染與侵襲性黴菌感染之分析
11. 初探新冠疫苗對不同宿主的免疫反應
12. 溶血磷脂醯膽鹼誘導肝臟ApoE醣基化及功能障礙:一種陰電性低密度脂蛋白在代謝症候群病人體內生合成的機制
13. 桌遊介入對長照機構高齡者 認知功能與孤寂感之效益探討
14. 桌遊對改善輕微失智老年人憂鬱與認知功能之成效:系統性文獻回顧
15. 接受化學治療肺癌病人癌因性疲憊與失志之關聯: 自我慈悲為中介變項