請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84480完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐莞曾(Wan-Tseng Hsu) | |
| dc.contributor.author | Hsin-Chung Chen | en |
| dc.contributor.author | 陳信中 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:12:56Z | - |
| dc.date.copyright | 2022-10-17 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-25 | |
| dc.identifier.citation | 1. Malakar, A.K., et al., A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol, 2019. 234(10): p. 16812. 2. Reed, G.W., et al., Acute myocardial infarction. Lancet, 2017. 389(10065): p. 197. 3. Velagaleti, R.S., et al., Long-term trends in the incidence of heart failure after myocardial infarction. Circulation, 2008. 118(20): p. 2057. 4. Bahit, M.C., et al., Post-Myocardial Infarction Heart Failure. JACC Heart Fail, 2018. 6(3): p. 179. 5. Coulombe, K.L.K., et al., Heart Regeneration with Engineered Myocardial Tissue. Annual Review of Biomedical Engineering, 2014. 16(1): p. 1. 6. Milutinović, A., et al., Pathogenesis of atherosclerosis in the tunica intima, media, and adventitia of coronary arteries: An updated review. Bosn J Basic Med Sci, 2020. 20(1): p. 21. 7. Libby, P., et al., Atherosclerosis. Nat Rev Dis Primers, 2019. 5(1): p. 56. 8. Ganesan, K., et al., Impact of consumption and cooking manners of vegetable oils on cardiovascular diseases- A critical review. Trends in Food Science & Technology, 2018. 71: p. 132. 9. Heusch, G., et al., The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J, 2017. 38(11): p. 774. 10. Chen, Q.M., Nrf2 for protection against oxidant generation and mitochondrial damage in cardiac injury. Free Radic Biol Med, 2022. 179: p. 133. 11. Tajabadi, M., et al., Regenerative strategies for the consequences of myocardial infarction: Chronological indication and upcoming visions. Biomed Pharmacother, 2022. 146: p. 112584. 12. Zhang, L., et al., Biochemical basis and metabolic interplay of redox regulation. Redox Biol, 2019. 26: p. 101284. 13. Dubois-Deruy, E., et al., Oxidative Stress in Cardiovascular Diseases. Antioxidants, 2020. 9(9): p. 864. 14. Andreadou, I., et al., Thiol-based redox-active proteins as cardioprotective therapeutic agents in cardiovascular diseases. Basic Res Cardiol, 2021. 116(1): p. 44. 15. Dorn, G.W., 2nd, et al., Mitochondrial biogenesis and dynamics in the developing and diseased heart. Genes Dev, 2015. 29(19): p. 1981. 16. Lopaschuk, G.D., Metabolic Modulators in Heart Disease: Past, Present, and Future. Can J Cardiol, 2017. 33(7): p. 838. 17. Evans, R.D., et al., The role of triacylglycerol in cardiac energy provision. Biochim Biophys Acta, 2016. 1861(10): p. 1481. 18. Bugger, H., et al., Mitochondrial ROS in myocardial ischemia reperfusion and remodeling. Biochim Biophys Acta Mol Basis Dis, 2020. 1866(7): p. 165768. 19. Ramachandra, C.J.A., et al., Mitochondria in acute myocardial infarction and cardioprotection. EBioMedicine, 2020. 57: p. 102884. 20. Kumar, V.K., et al., Mitochondrial Membrane Intracellular Communication in Healthy and Diseased Myocardium. Front Cell Dev Biol, 2020. 8: p. 609241. 21. Zorov, D.B., et al., Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev, 2014. 94(3): p. 909. 22. Poznyak, A.V., et al., Oxidative Stress and Antioxidants in Atherosclerosis Development and Treatment. Biology (Basel), 2020. 9(3): p. 60. 23. Montezano, A.C., et al., Reactive oxygen species and endothelial function--role of nitric oxide synthase uncoupling and Nox family nicotinamide adenine dinucleotide phosphate oxidases. Basic Clin Pharmacol Toxicol, 2012. 110(1): p. 87. 24. Li, H., et al., Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis, 2014. 237(1): p. 208. 25. Fihn, S.D., et al., 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol, 2012. 60(24): p. e44. 26. Douglas L. Mann, D.P.Z.P.L.R.O.B., et al., Braunwald’s heart disease : a textbook of cardiovascular medicine. 2022: Twelfth edition. Philadelphia, PA : Elsevier/Saunders, [2022]. 27. Braun, M.M., et al., Stable Coronary Artery Disease: Treatment. Am Fam Physician, 2018. 97(6): p. 376. 28. Wu, K.K., Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite. Front Pharmacol, 2021. 12: p. 759199. 29. Cho, J.Y., et al., 5-Methoxytryptophan: A game changer in the management of post-myocardial infarction? J Mol Cell Cardiol, 2021. 160: p. 71. 30. Ho, Y.C., et al., A Novel Protective Function of 5-Methoxytryptophan in Vascular Injury. Sci Rep, 2016. 6: p. 25374. 31. Lin, Y.H., et al., 5-methoxytryptophan is a potential marker for post-myocardial infarction heart failure - a preliminary approach to clinical utility. Int J Cardiol, 2016. 222: p. 895. 32. Saccani, S., et al., p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat Immunol, 2002. 3(1): p. 69. 33. Gustin, J.A., et al., Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/MSK1 signaling pathway in endothelial cells. Am J Physiol Cell Physiol, 2004. 286(3): p. C547. 34. Wu, K.K., et al., 5-methoxytryptophan: an arsenal against vascular injury and inflammation. J Biomed Sci, 2020. 27(1): p. 79. 35. Wu, K.K., et al., 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis. J Biomed Sci, 2014. 21(1): p. 17. 36. Chu, L.Y., et al., Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation. PLoS One, 2016. 11(3): p. e0152166. 37. Hansson, G.K., et al., The immune system in atherosclerosis. Nature Immunology, 2011. 12(3): p. 204. 38. Eming, S.A., et al., Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med, 2014. 6(265): p. 265sr6. 39. Gibb, A.A., et al., Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation. Circ Res, 2020. 127(3): p. 427. 40. Henderson, N.C., et al., Fibrosis: from mechanisms to medicines. Nature, 2020. 587(7835): p. 555. 41. Hsu, W.T., et al., 5-Methoxytryptophan attenuates postinfarct cardiac injury by controlling oxidative stress and immune activation. J Mol Cell Cardiol, 2021. 158: p. 101. 42. Tong, M., et al., 5-methoxytryptophan alleviates liver fibrosis by modulating FOXO3a/miR-21/ATG5 signaling pathway mediated autophagy. Cell Cycle, 2021. 20(7): p. 676. 43. Chen, D.Q., et al., Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan. Nat Commun, 2019. 10(1): p. 1476. 44. Fang, L., et al., Endogenous tryptophan metabolite 5-Methoxytryptophan inhibits pulmonary fibrosis by downregulating the TGF-β/SMAD3 and PI3K/AKT signaling pathway. Life Sci, 2020. 260: p. 118399. 45. Colliva, A., et al., Endothelial cell-cardiomyocyte crosstalk in heart development and disease. J Physiol, 2020. 598(14): p. 2923. 46. Eelen, G., et al., Endothelial Cell Metabolism. Physiol Rev, 2018. 98(1): p. 3. 47. Tang, X., et al., Mitochondria, endothelial cell function, and vascular diseases. Front Physiol, 2014. 5: p. 175. 48. Yuan, C., et al., Vascular calcification: New insights into endothelial cells. Microvasc Res, 2021. 134: p. 104105. 49. Siti, H.N., et al., The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol, 2015. 71: p. 40. 50. Förstermann, U., et al., Nitric oxide synthases: regulation and function. Eur Heart J, 2012. 33(7): p. 829. 51. Krüger-Genge, A., et al., Vascular Endothelial Cell Biology: An Update. Int J Mol Sci, 2019. 20(18): p. 4411. 52. Burgoyne, J.R., et al., Hydrogen peroxide sensing and signaling by protein kinases in the cardiovascular system. Antioxid Redox Signal, 2013. 18(9): p. 1042. 53. Jiang, F., et al., Monotropein alleviates H2O2‑induced inflammation, oxidative stress and apoptosis via NF‑κB/AP‑1 signaling. Mol Med Rep, 2020. 22(6): p. 4828. 54. Patel, H., et al., Induced peroxidase and cytoprotective enzyme expressions support adaptation of HUVECs to sustain subsequent H2O2 exposure. Microvasc Res, 2016. 103: p. 1. 55. Surico, D., et al., Human Chorionic Gonadotropin Protects Vascular Endothelial Cells from Oxidative Stress by Apoptosis Inhibition, Cell Survival Signalling Activation and Mitochondrial Function Protection. Cell Physiol Biochem, 2015. 36(6): p. 2108. 56. Warnes, G., Flow cytometric detection of hyper-polarized mitochondria in regulated and accidental cell death processes. Apoptosis, 2020. 25(7-8): p. 548. 57. Gan, I., et al., Mitochondrial permeability regulates cardiac endothelial cell necroptosis and cardiac allograft rejection. Am J Transplant, 2019. 19(3): p. 686. 58. Elbatreek, M.H., et al., NOX Inhibitors: From Bench to Naxibs to Bedside. Handb Exp Pharmacol, 2021. 264: p. 145. 59. Lassègue, B., et al., Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res, 2012. 110(10): p. 1364. 60. Niu, G., et al., Apoptosis imaging: beyond annexin V. J Nucl Med, 2010. 51(11): p. 1659. 61. Ghavami, S., et al., Apoptosis and cancer: mutations within caspase genes. J Med Genet, 2009. 46(8): p. 497. 62. Petrie, E.J., et al., The Structural Basis of Necroptotic Cell Death Signaling. Trends Biochem Sci, 2019. 44(1): p. 53. 63. Zhang, T., et al., CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med, 2016. 22(2): p. 175. 64. Zhang, D.W., et al., RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science, 2009. 325(5938): p. 332. 65. Wang, Z., et al., Progress in studies of necroptosis and its relationship to disease processes. Pathol Res Pract, 2018. 214(11): p. 1749. 66. Rambold, A.S., et al., Mitochondrial Dynamics at the Interface of Immune Cell Metabolism and Function. Trends Immunol, 2018. 39(1): p. 6. 67. Sack, M.N., et al., Basic Biology of Oxidative Stress and the Cardiovascular System: Part 1 of a 3-Part Series. J Am Coll Cardiol, 2017. 70(2): p. 196. 68. Cadenas, S., et al., Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart disease. Cardiovascular Research, 2010. 88(2): p. 219. 69. Cadenas, S., ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free Radic Biol Med, 2018. 117: p. 76. 70. Chandel, N.S., et al., Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci U S A, 1998. 95(20): p. 11715. 71. Hira, S., et al., EAE-induced upregulation of mitochondrial MnSOD is associated with increases of mitochondrial SGK1 and Tom20 protein in the mouse kidney cortex. J Physiol Sci, 2019. 69(5): p. 723. 72. Hjelmeland, A.B., et al., SOD2 acetylation and deacetylation: Another tale of Jekyll and Hyde in cancer. Proc Natl Acad Sci U S A, 2019. 116(47): p. 23376. 73. Tsai, Y.T., et al., Superoxide Dismutase 2 (SOD2) in Vascular Calcification: A Focus on Vascular Smooth Muscle Cells, Calcification Pathogenesis, and Therapeutic Strategies. Oxid Med Cell Longev, 2021. 2021: p. 6675548. 74. Dong, S., et al., 5-Hydroxytryptamine (5-HT)-exacerbated DSS-induced colitis is associated with elevated NADPH oxidase expression in the colon. J Cell Biochem, 2019. 120(6): p. 9230. 75. Lee, D.Y., et al., Nox4 NADPH oxidase mediates peroxynitrite-dependent uncoupling of endothelial nitric-oxide synthase and fibronectin expression in response to angiotensin II: role of mitochondrial reactive oxygen species. J Biol Chem, 2013. 288(40): p. 28668. 76. Čapek, J., et al., Detection of Oxidative Stress Induced by Nanomaterials in Cells-The Roles of Reactive Oxygen Species and Glutathione. Molecules, 2021. 26(16): p. 4710. 77. Sun, D., et al., Salvianolate ameliorates renal tubular injury through the Keap1/Nrf2/ARE pathway in mouse kidney ischemia-reperfusion injury. J Ethnopharmacol, 2022. 293: p. 115331. 78. Majtnerová, P., et al., An overview of apoptosis assays detecting DNA fragmentation. Mol Biol Rep, 2018. 45(5): p. 1469. 79. Pietkiewicz, S., et al., Quantification of apoptosis and necroptosis at the single cell level by a combination of Imaging Flow Cytometry with classical Annexin V/propidium iodide staining. J Immunol Methods, 2015. 423: p. 99. 80. Wang, X., et al., Lactonic sophorolipid-induced apoptosis in human HepG2 cells through the Caspase-3 pathway. Appl Microbiol Biotechnol, 2021. 105(5): p. 2033. 81. Wurm, C.A., et al., Nanoscale distribution of mitochondrial import receptor Tom20 is adjusted to cellular conditions and exhibits an inner-cellular gradient. Proc Natl Acad Sci U S A, 2011. 108(33): p. 13546. 82. Yan, C., et al., PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis. Autophagy, 2020. 16(3): p. 419. 83. Dikalova, A.E., et al., Sirt3 Impairment and SOD2 Hyperacetylation in Vascular Oxidative Stress and Hypertension. Circ Res, 2017. 121(5): p. 564. 84. Wei, H., et al., Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced inflammatory responses in vivo. Am J Physiol Heart Circ Physiol, 2011. 301(3): p. H712. 85. Al-Zubaidi, U., et al., The spatio-temporal dynamics of mitochondrial membrane potential during oocyte maturation. Mol Hum Reprod, 2019. 25(11): p. 695. 86. Perelman, A., et al., JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis, 2012. 3(11): p. e430. 87. Liu, Z., et al., A FRET Based Two-Photon Fluorescent Probe for Visualizing Mitochondrial Thiols of Living Cells and Tissues. Sensors (Basel), 2020. 20(6). 88. Jin, J.Y., et al., Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin, 2021. 42(5): p. 655. 89. Duan, C., et al., Mitochondrial Drp1 recognizes and induces excessive mPTP opening after hypoxia through BAX-PiC and LRRK2-HK2. Cell Death Dis, 2021. 12(11): p. 1050. 90. Johnson, L.V., et al., Localization of mitochondria in living cells with rhodamine 123. Proc Natl Acad Sci U S A, 1980. 77(2): p. 990. 91. Chazotte, B., Labeling mitochondria with MitoTracker dyes. Cold Spring Harb Protoc, 2011. 2011(8): p. 990. 92. Harwig, M.C., et al., Methods for imaging mammalian mitochondrial morphology: A prospective on MitoGraph. Anal Biochem, 2018. 552: p. 81. 93. Nasoni, M.G., et al., Melatonin reshapes the mitochondrial network and promotes intercellular mitochondrial transfer via tunneling nanotubes after ischemic-like injury in hippocampal HT22 cells. J Pineal Res, 2021. 71(1): p. e12747. 94. Koopman, W.J., et al., Simultaneous quantitative measurement and automated analysis of mitochondrial morphology, mass, potential, and motility in living human skin fibroblasts. Cytometry A, 2006. 69(1): p. 1. 95. Chuang, J.I., et al., Melatonin prevents the dynamin-related protein 1-dependent mitochondrial fission and oxidative insult in the cortical neurons after 1-methyl-4-phenylpyridinium treatment. J Pineal Res, 2016. 61(2): p. 230. 96. Lin, H., et al., Inhibition of DRP-1-Dependent Mitophagy Promotes Cochlea Hair Cell Senescence and Exacerbates Age-Related Hearing Loss. Front Cell Neurosci, 2019. 13: p. 550. 97. Wu, K.K., Control of Mesenchymal Stromal Cell Senescence by Tryptophan Metabolites. Int J Mol Sci, 2021. 22(2). 98. Wang, J.L., et al., A bright, red-emitting water-soluble BODIPY fluorophore as an alternative to the commercial Mito Tracker Red for high-resolution mitochondrial imaging. J Mater Chem B, 2021. 9(41): p. 8639. 99. Aula, S., et al., Biophysical, biopharmaceutical and toxicological significance of biomedical nanoparticles. RSC Advances, 2015. 5(59): p. 47830. 100. Tian, M., et al., Fluorescent Probes for the Visualization of Cell Viability. Acc Chem Res, 2019. 52(8): p. 2147. 101. Zorova, L.D., et al., Mitochondrial membrane potential. Anal Biochem, 2018. 552: p. 50. 102. Mohanty, S., et al., RETRA induces necroptosis in cervical cancer cells through RIPK1, RIPK3, MLKL and increased ROS production. Eur J Pharmacol, 2022. 920: p. 174840. 103. Nguyen, N.T., et al., Oxidative Stress Related to Plasmalemmal and Mitochondrial Phosphate Transporters in Vascular Calcification. Antioxidants (Basel), 2022. 11(3): p. 494. 104. Sies, H., Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress. Redox Biol, 2017. 11: p. 613. 105. Lindsey, M.L., et al., Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol, 2018. 314(4): p. H812. 106. Association, A.D., 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care, 2020. 44(Supplement_1): p. S15. 107. Chen, Z., et al., Pharmacological inhibition of GLUT1 as a new immunotherapeutic approach after myocardial infarction. Biochem Pharmacol, 2021. 190: p. 114597. 108. Uebelhoer, M., et al., Cross-talk between signaling and metabolism in the vasculature. Vascul Pharmacol, 2016. 83: p. 4. 109. Mertens, S., et al., Energetic response of coronary endothelial cells to hypoxia. Am J Physiol, 1990. 258(3 Pt 2): p. H689. 110. Liu, W., et al., AM1241 alleviates myocardial ischemia-reperfusion injury in rats by enhancing Pink1/Parkin-mediated autophagy. Life Sci, 2021. 272: p. 119228. 111. Qiu, X., et al., RIP3 is an upregulator of aerobic metabolism and the enhanced respiration by necrosomal RIP3 feeds back on necrosome to promote necroptosis. Cell Death Differ, 2018. 25(5): p. 821. 112. Groschner, L.N., et al., Endothelial mitochondria--less respiration, more integration. Pflugers Arch, 2012. 464(1): p. 63. 113. Kim, Y.M., et al., ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis. Am J Physiol Cell Physiol, 2017. 312(6): p. C749. 114. Sun, X., et al., NOX4- and Nrf2-mediated oxidative stress induced by silver nanoparticles in vascular endothelial cells. J Appl Toxicol, 2017. 37(12): p. 1428. 115. Kong, L.J., et al., Muramyl Dipeptide Induces Reactive Oxygen Species Generation Through the NOD2/COX-2/NOX4 Signaling Pathway in Human Umbilical Vein Endothelial Cells. J Cardiovasc Pharmacol, 2018. 71(6): p. 352. 116. Gray, S.P., et al., Reactive Oxygen Species Can Provide Atheroprotection via NOX4-Dependent Inhibition of Inflammation and Vascular Remodeling. Arterioscler Thromb Vasc Biol, 2016. 36(2): p. 295. 117. He, W., et al., NOX4 rs11018628 polymorphism associates with a decreased risk and better short-term recovery of ischemic stroke. Exp Ther Med, 2018. 16(6): p. 5258. 118. Drummond, G.R., et al., Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov, 2011. 10(6): p. 453. 119. Guzik, T.J., et al., Calcium-dependent NOX5 nicotinamide adenine dinucleotide phosphate oxidase contributes to vascular oxidative stress in human coronary artery disease. J Am Coll Cardiol, 2008. 52(22): p. 1803. 120. Yang, Z., et al., RIP3 targets pyruvate dehydrogenase complex to increase aerobic respiration in TNF-induced necroptosis. Nat Cell Biol, 2018. 20(2): p. 186. 121. Chouchani, E.T., et al., Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature, 2014. 515(7527): p. 431. 122. Chouchani, E.T., et al., A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury. Cell Metab, 2016. 23(2): p. 254. 123. Angeli, J.P.F., et al., Ferroptosis Inhibition: Mechanisms and Opportunities. Trends Pharmacol Sci, 2017. 38(5): p. 489. 124. Gao, M., et al., Role of Mitochondria in Ferroptosis. Mol Cell, 2019. 73(2): p. 354. 125. Vanden Berghe, T., et al., Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ, 2010. 17(6): p. 922. 126. Zhu, Y., et al., Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy. Apoptosis, 2020. 25(5-6): p. 321. 127. Zhu, Y., et al., Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2-induced PSMB5 in endothelial cells. Drug Dev Res, 2019. 80(4): p. 481. 128. Chen, H.L., et al., Restoration of hydroxyindole O-methyltransferase levels in human cancer cells induces a tryptophan-metabolic switch and attenuates cancer progression. J Biol Chem, 2018. 293(28): p. 11131. 129. Chen, C.H., et al., Tryptophan metabolite 5-methoxytryptophan ameliorates arterial denudation-induced intimal hyperplasia via opposing effects on vascular endothelial and smooth muscle cells. Aging (Albany NY), 2019. 11(19): p. 8604. 130. Wang, Y.F., et al., Endothelium-Derived 5-Methoxytryptophan Is a Circulating Anti-Inflammatory Molecule That Blocks Systemic Inflammation. Circ Res, 2016. 119(2): p. 222. 131. Khan, S.A., et al., N-Acetylcysteine for Cardiac Protection During Coronary Artery Reperfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Cardiovasc Med, 2021. 8: p. 752939. 132. Kumar, S.K., et al., Endocan alters nitric oxide production in endothelial cells by targeting AKT/eNOS and NFkB/iNOS signaling. Nitric Oxide, 2021. 117: p. 26. 133. Cao, Y., et al., The use of human umbilical vein endothelial cells (HUVECs) as an in vitro model to assess the toxicity of nanoparticles to endothelium: a review. J Appl Toxicol, 2017. 37(12): p. 1359. 134. Kocherova, I., et al., Human Umbilical Vein Endothelial Cells (HUVECs) Co-Culture with Osteogenic Cells: From Molecular Communication to Engineering Prevascularised Bone Grafts. J Clin Med, 2019. 8(10): p. 1602. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84480 | - |
| dc.description.abstract | 研究背景 冠狀動脈疾病 (coronary artery disease, CAD) 主要是由冠狀動脈阻塞導致，儘管目前可透過經皮冠狀動脈介入術與冠狀動脈繞道手術進行治療，但所產生的心肌損傷依舊無法停止，且後續引發心臟功能失調的病理機制涉及多種層面，以致全球的住院率與致死率居高不下，因此需要新穎的治療策略。 研究目的 根據先導性研究，5-甲氧基色胺酸 (5-Methoxytryptophan, 5-MTP) 在氧化壓力上扮演調控角色，而產生活性氧物質的主要來源為粒線體。為了探討5-MTP的作用機制，以人類臍靜脈血管內皮細胞 (human umbilical vein endothelial cell, HUVEC) 氧化壓力平台測試粒線體的各項指標。本研究建立HUVEC氧化壓力平台，進而以此平台評估5-MTP於HUVEC之調控粒線體功能與血管保護效果。 實驗方法 以剝奪血清與生長因子並給予100 μM的過氧化氫 (hydrogen peroxide, H2O2)來建立HUVEC氧化壓力平台，而5-MTP的配置濃度則是依據先導性研究的心肌梗塞大鼠之5-MTP血中濃度，平均濃度為20 μg/mL，以此濃度為治療濃度。實驗分成以下4組： 1. Control (Ctl) 組：定期更換新鮮Complete-Endothelial Cell Growth medium 2 (ECGM2) 培養基。 2. Ctl + 5-MTP組：5-MTP預處理24小時後更換新鮮ECGM2培養基。 3. ROS組：剝奪血清與生長因子且同時添加100 μM的H2O2反應3或4小時。 4. ROS + 5-MTP組：5-MTP預處理24小時後進行剝奪血清與生長因子且同時添加100 μM的H2O2反應3或4小時。 為了評估粒線體的各項指標，透過mitobright、mtSOX與MT-1三種螢光染劑，分別檢測粒線體形變、超氧陰離子 (O2–) 與膜電位的變化。 結果與討論 實驗結果顯示，ROS組相比於Ctl組，其網狀的健康粒線體呈現統計顯著性的下降，而顆粒狀的受損粒線體則統計顯著性的上升，且伴隨O2–過度增加與粒線體膜電位異常。經由5-MTP預處理治療，能統計顯著性的減緩粒線體片段化、降低O2–含量，並減少膜電位異常。在西方墨點法分析中，參與5-MTP之生合成路徑的羥吲哚O-甲基轉移酶 (hydroxyindole O-methyltransferase, HIOMT) 呈現統計顯著性的上升。實驗結果指出ROS組與ROS + 5-MTP組皆能夠顯著提升HIOMT的表現量，但是這兩組之間無統計顯著性差異。在細胞存活率分析上，實驗結果指出ROS + 5-MTP組相較於ROS組，能統計顯著性的降低細胞死亡。粒線體的O2–與膜電位主要受電子傳遞鏈與能量代謝影響，而粒線體形變異常可能與dynamin-related protein 1過度活化而誘發顆粒狀型態的粒線體有關，推測5-MTP參與這些訊息路徑，往後若需釐清5-MTP作用於HUVEC之詳細機轉，可從以上途徑深入探討。 結論 從各項研究結果指出，5-MTP的治療機轉可藉由減緩粒線體的O2–含量，並減少膜電位異常與形變來達到氧化壓力下之血管保護效果。 | zh_TW |
| dc.description.abstract | Background Coronary artery disease (CAD) is caused by coronary artery occlusion. Although percutaneous coronary intervention and coronary artery bypass surgery are possible treatments, the myocardial damage cannot be reversed. The subsequent pathological mechanisms of cardiac dysfunction include multiple levels, leading to high rates of hospitalization and mortality worldwide. To effectively treat CAD, innovative therapies are required. Objectives 5-Methoxytryptophan (5-MTP) regulates oxidative stress, and the mitochondria are the primary sources of reactive oxygen species. A human umbilical vein endothelial cell (HUVEC) oxidative stress platform was used to evaluate multiple mitochondrial indicators and investigate the mechanisms of 5-MTP. We explored the influence of 5-MTP on mitochondrial function and the vasoprotective effect in a HUVEC oxidative stress platform. Methods To create a HUVEC oxidative stress platform, HUVECs were exposed to 100 μM H2O2 in a serum and growth factor deprivation (SGFD) medium. The concentration of 5-MTP was 20 μg/mL and was based on the mean plasma concentration of 5-MTP in myocardial infarction rats. Cells were divided into four groups: (1) cells in the control (Ctl) group were supplied with fresh endothelial cell growth medium 2 (ECGM2); (2) cells in the Ctl + 5-MTP group received 5-MTP treatment for 24 h in ECGM2; (3) cells in the ROS group were subjected to SGFD plus 100 μM H2O2 for 3 or 4 h; (4) cells in the ROS + 5-MTP group were exposed to 5-MTP therapy for 24 h before oxidative damage for 3 or 4 h. Three fluorescent dyes, mitobright, mtSOX, and MT-1, were used to measure changes in the morphology of mitochondria, superoxide (O2–), and membrane potential, respectively. Results and Discussion The results revealed that the healthy reticulated mitochondria decreased in number in the ROS group. However, the level of granular damaged mitochondria increased, the level of O2– increased excessively, and the aberrant mitochondrial membrane potential decreased. 5-MTP alleviated morphological abnormalities in mitochondria, the level of O2– and the mitochondrial membrane potential. According to a Western blot analysis, hydroxyindole O-methyltransferase (HIOMT), which is involved in the biosynthesis of 5-MTP, was affected by 5-MTP. The results demonstrated that HIOMT expression could be significantly increased by both the ROS and the ROS + 5-MTP groups. At the same time, no statistically significant difference was observed between the ROS and the ROS + 5-MTP groups. Regarding cell viability, the results revealed that the ROS + 5-MTP group could considerably reduce cell death. The electron transport chain and energy metabolism primarily affected the superoxide and mitochondrial membrane potential, and the abnormal mitochondrial morphology may be linked to the excessive activation of dynamin-related protein 1 to induce mitochondrial morphological changes. To fully comprehend the mechanism of 5-MTP in HUVECs, these pathways should be evaluated in future research. Conclusion According to our results, the therapeutic effects of 5-MTP involve suppressing superoxide production, abnormal membrane potential, and morphological alterations in the mitochondria to achieve vasoprotection in response to oxidative stress. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:12:56Z (GMT). No. of bitstreams: 1 U0001-2309202214322700.pdf: 21740321 bytes, checksum: 9b1837fe804373e1d150755c8d6034aa (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書 ii 誌謝 iii 中文摘要 iv Abstract vi 圖目錄 xi 表目錄 xii 第一章、緒論 1 壹、 心血管系統、冠狀動脈硬化與心肌梗塞簡介 1 一、 心血管系統 1 二、 冠狀動脈硬化 2 三、 心肌梗塞 3 貳、 冠狀動脈疾病之病理機制、臨床治療與瓶頸 3 一、 冠狀動脈疾病之病理機制 3 二、 冠狀動脈疾病之臨床治療與瓶頸 6 參、5-甲氧基色胺酸 (5-Methoxytryptophan, 5-MTP) 的治療潛力 7 一、抗發炎效果 8 二、保護血管的生理功能 9 三、抗纖維化能力 9 肆、血管內皮細胞之生理功能與冠狀動脈疾病的關聯性 10 一、調控氧化壓力 10 二、避免發炎細胞過度活化 11 三、促進血管新生 11 四、減少血小板過度凝集 11 五、促進血管平滑肌舒張 12 六、釋放多種生長因子 12 伍、血管內皮細胞於氧化壓力下之影響 12 陸、5-MTP之先導性研究與可能調控機轉 13 一、5-MTP於心肌梗塞治療之先導性研究 13 二、5-MTP之可能調控機轉 14 柒、促氧化媒介、細胞凋亡媒介與粒線體之抗氧化媒介常見分析方法 17 一、促氧化媒介 17 二、細胞凋亡媒介 17 三、粒線體之抗氧化媒介 18 捌、當前研究限制 19 一、缺乏5-MTP作用於血管內皮細胞上的深入研究 19 二、缺乏5-MTP作用於促氧化媒介與粒線體的相關機制 19 玖、研究假說與目的 20 第二章、研究方法 21 壹、建立血管內皮細胞之氧化壓力平台與測試5-MTP之能量代謝調控效應 21 貳、5-MTP之血管內皮細胞粒線體調控 26 參、5-MTP之血管內皮細胞保護效果 40 肆、統計分析 43 第三章、實驗結果 44 壹、建立血管內皮細胞之氧化壓力平台與測試5-MTP之能量代謝調控效應 44 貳、5-MTP之血管內皮細胞粒線體調控 44 參、5-MTP之血管內皮細胞保護效果 49 第四章、討論 50 壹、人類臍靜脈血管內皮細胞 (human umbilical vein endothelial cell, HUVEC) 之氧化壓力平台的研究限制 50 貳、能量代謝 50 參、氧化壓力 52 肆、過極化現象 54 伍、粒線體分裂蛋白與上游訊息路徑 55 陸、細胞死亡途徑與5-MTP之生合成路徑 56 柒、當前研究限制與解決之道 57 第五章、結論與展望 60 第六章、圖 61 參考文獻 81 附錄 91 壹、 專有名詞之中英文暨縮寫對照表 91 貳、 西方墨點法原圖-促氧化酶 94 參、 西方墨點法原圖-細胞壞死性凋亡蛋白質 95 肆、 西方墨點法原圖-粒線體完整性與功能性蛋白質 96 伍、 西方墨點法原圖-5-MTP之生合成酶 97 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討 5-甲氧基色胺酸之血管保護療效與抗氧化能力 | zh_TW |
| dc.title | Exploration of Vasoprotective and Superoxide-Reducing Effects of 5-Methoxytryptophan | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林秀芳(Shaw-Fang Yet),徐千彝(Chien-Yi Hsu),魏子堂(Tzu-Tang Wei) | |
| dc.subject.keyword | 冠狀動脈疾病,5-甲氧基色胺酸,血管內皮細胞,粒線體,超氧陰離子,過極化, | zh_TW |
| dc.subject.keyword | coronary artery disease,5-Methoxytryptophan,endothelial cell,mitochondria,superoxide,hyperpolarization, | en |
| dc.relation.page | 97 | |
| dc.identifier.doi | 10.6342/NTU202203911 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-09-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| dc.date.embargo-lift | 2027-09-25 | - |
| 顯示於系所單位： | 藥學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2309202214322700.pdf 目前未授權公開取用 | 21.23 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。