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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳玉怜 | zh_TW |
| dc.contributor.advisor | Yuh-Lien Chen | en |
| dc.contributor.author | 陳雅君 | zh_TW |
| dc.contributor.author | Ya-Chun Chen | en |
| dc.date.accessioned | 2025-09-09T16:11:17Z | - |
| dc.date.available | 2025-09-10 | - |
| dc.date.copyright | 2025-09-09 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-07-17 | - |
| dc.identifier.citation | Almutairi M, Almutairi AA, Alodhialah AM. The influence of lifestyle modifications on cardiovascular outcomes in older adults: dindings from a cross-sectional study. Life (Basel). 2025; 15: 87.
Arjmand B, Safavi M, Heidari R, Aghayan H, S TB, Dehghani S, et al. Concomitant transurethral and transvaginal-periurethral injection of autologous adipose derived stem cells for treatment of female stress urinary incontinence: a phase one clinical trial. Acta Med Iran. 2017; 55: 368-74. Balluz L, Wen XJ, Town M, Shire JD, Qualter J, Mokdad A. Ischemic heart disease and ambient air pollution of particulate matter 2.5 in 51 counties in the U.S, Public Health Rep. 2007; 122: 626-33. Basith S, Manavalan B, Shin TH, Park CB, Lee WS, Kim J, et al. The impact of fine particulate matter 2.5 on the cardiovascular system: a review of the invisible killer. Nanomaterials (Basel). 2022; 12: 2656. Batty M, Bennett MR, Yu E. The role of oxidative stress in atherosclerosis. Cells. 2022; 11: 3843. Brady NR, Hamacher-Brady A, Gottlieb RA. Proapoptotic BCL-2 family members and mitochondrial dysfunction during ischemia/reperfusion injury, a study employing cardiac HL-1 cells and GFP biosensors. Biochim Biophys Acta. 2006; 1757: 667-78. Brochu P, Bouchard M, Haddad S. Physiological daily inhalation rates for health risk assessment in overweight/obese children, adults, and elderly. Risk Anal. 2014; 34: 567-82. Cai Y, Li J, Jia C, He Y, Deng C. Therapeutic applications of adipose cell-free derivatives: a review. Stem Cell Res Ther. 2020; 11: 312. Cao J, Qin G, Shi R, Bai F, Yang G, Zhang M, et al. Overproduction of reactive oxygen species and activation of MAPKs are involved in apoptosis induced by PM2.5 in rat cardiac H9c2 cells. J Appl Toxicol. 2016; 36: 609-17. Chen CC, Wang YR, Liu JS, Chang HY, Guo YL, Chen PC. Burden of cardiovascular disease attributable to long-term exposure to ambient PM2.5 concentration and the cost-benefit analysis for the optimal control level. Sci Total Environ. 2023; 892: 164767. Chen D, Li X, Zhang LT, Zhu M, Gao L. A high-fat diet impairs mitochondrial biogenesis, mitochondrial dynamics, and the respiratory chain complex in rat myocardial tissues. J Cell Biochem. 2018; 119: 9602. Chen G, Kroemer G, Kepp O. Mitophagy: An emerging role in aging and age-associated diseases. Front Cell Dev Biol. 2020; 8: 200. Chen SS, Chen WQ, Li ZP, Yue JW, Yung KKL, Li RJ. Regulation of PM2.5 on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol. J Environ Sci (China). 2024; 138: 288-300. Chen YR, Zweier JL. Cardiac mitochondria and reactive oxygen species generation. Circ Res. 2014; 114: 524-37. Cheng QQ, Wan YW, Yang WM, Tian MH, Wang YC, He HY, et al. Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction. Acta Pharmacol Sin. 2020; 41: 1314-27. Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV. Human miR-221/222 in physiological and atherosclerotic vascular remodeling. Biomed Res Int. 2015; 2015: 354517. Condorelli G, Latronico MV, Cavarretta E. microRNAs in cardiovascular diseases: current knowledge and the road ahead. J Am Coll Cardiol. 2014; 63: 2177-87. Corsten MF, Heggermont W, Papageorgiou AP, Deckx S, Tijsma A, Verhesen W, et al. The microRNA-221/-222 cluster balances the antiviral and inflammatory response in viral myocarditis. Eur Heart J. 2015; 36: 2909-19. Cosselman KE, Navas-Acien A, Kaufman JD. Environmental factors in cardiovascular disease. Nat Rev Cardiol. 2015; 12: 627-42. D'Oria R, Schipani R, Leonardini A, Natalicchio A, Perrini S, Cignarelli A, et al. The role of oxidative stress in cardiac disease: from physiological response to injury factor. Oxid Med Cell Longev. 2020; 2020: 5732956. Dong L, Sun W, Li F, Shi M, Meng X, Wang C, et al. The harmful effects of acute PM(2.5) exposure to the heart and a novel preventive and therapeutic function of CEOs. Sci Rep. 2019; 9: 3495. Dubois-Deruy E, Cuvelliez M, Fiedler J, Charrier H, Mulder P, Hebbar E, et al. MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure. Sci Rep. 2017; 7: 14747. Fernandez O, Izquierdo G, Fernandez V, Leyva L, Reyes V, Guerrero M, et al. Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: a triple blinded, placebo controlled, randomized phase I/II safety and feasibility study. PLoS One. 2018; 13: e0195891. Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin GA, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene. 2008; 27: 5651-61. Girona J, Soler O, Samino S, Junza A, Martínez-Micaelo N, García-Altares M, et al. Lipidomics reveals myocardial lipid composition in a murine model of insulin resistance induced by a high-fat diet. Int J Mol Sci. 2024; 25: 2702. Guo Q, Li D, Luo X, Yuan Y, Li T, Liu H, et al. The regulatory network and potential role of LINC00973-miRNA-mRNA ceRNA in the progression of non-small-cell lung cancer. Front Immunol. 2021; 12: 684807. Hata A. Functions of microRNAs in cardiovascular biology and disease. Annu Rev Physiol. 2013; 75: 69-93. Hu Q, Zhang H, Gutierrez Cortes N, Wu D, Wang P, Zhang J, et al. Increased Drp1 acetylation by lipid overload induces cardiomyocyte death and heart dysfunction. Circ Res. 2020; 126: 456-70. Hutcheson R, Rocic P. The metabolic syndrome, oxidative stress, environment, and cardiovascular disease: the great exploration. Exp Diabetes Res. 2012; 2012: 271028. IQAir. 2023 World Air Quality Report. Goldach, Switzerland: IQAir; 2024. Available from: https://www.iqair.com/world-air-quality-report Jiang F, Huang Q, Nian J, Yang S. miR-221/222/PUMA axis promotes oral squamous cell carcinoma apoptosis, Open J Stomatol. 2023; 13: 367-83. Jiang JJ, Li Y, Liang S, Sun BY, Shi YF, Xu Q, et al. Combined exposure of fine particulate matter and high-fat diet aggravate the cardiac fibrosis in C57BL/6J mice. J Hazard Mater. 2020; 391: 12033. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem cells. 2006; 24: 1294-301. Kim EH, Heo CY. Current applications of adipose-derived stem cells and their future perspectives. World J Stem Cells. 2014; 6: 65-8. Kim JB, Kim C, Choi E, Park S, Park H, Pak HN, et al. Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation. Toxicol Appl Pharmacol. 2012; 259: 66-73. Knowlton AA, Chen L, Malik ZA. Heart failure and mitochondrial dysfunction: the role of mitochondrial fission/fusion abnormalities and new therapeutic strategies. J Cardiovasc Pharmacol. 2014; 63: 196-206. Krittanawong C, Qadeer YK, Hayes RB, Wang Z, Thurston GD, Virani S, et al. PM2.5 and cardiovascular diseases: state-of-the-art review. Int J Cardiol Cardiovasc Risk Prev. 2023; 19: 200217. Kumar H, Ha DH, Lee EJ, Park JH, Shim JH, Ahn TK, et al. Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem Cell Res Ther. 2017; 8: 262. Lai TC, Lee TL, Chang YC, Chen YC, Lin SR, Lin SW, et al. MicroRNA-221/222 mediates ADSC-exosome-induced cardioprotection against ischemia/reperfusion by targeting PUMA and ETS-1. Front Cell Dev Biol. 2020; 8: 569150. Landrigan PJ, Fuller R, Acosta NJR, Adeyi O, Arnold R, Basu NN, et al. The lancet commission on pollution and health. Lancet. 2018; 391: 462-512. le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 2007; 26: 3699-708. Lee TL, Lai TC, Lin SR, Lin SW, Chen YC, Pu CM, et al. Conditioned medium from adipose-derived stem cells attenuates ischemia/reperfusion-induced cardiac injury through the microRNA-221/222/PUMA/ETS-1 pathway. Theranostics. 2021; 11: 3131-49. Lee TL, Shen WC, Chen YC, Lai TC, Lin SR, Lin SW, et al. Mir221- and mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway. Autophagy. 2024: 1-20. Li LY, Hu DY, Zhang WL, Cui LY, Jia X, Yang D, et al. Effect of short-term exposure to particulate air pollution on heart rate variability in normal-weight and obese adults. Environ Health. 2021; 20: 29. Li T, Mu N, Yin Y, Yu L, Ma H. Targeting AMP-activated protein kinase in aging-related cardiovascular diseases. Aging Dis. 2020; 11: 967-77. Li T, Providencia R, Mu N, Yin Y, Chen M, Wang YS, et al. Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2021; 20: 30. Liu CW, Sung HC, Lin SR, Wu CW, Lee CW, Lee IT, et al. Resveratrol attenuates ICAM-1 expression and monocyte adhesiveness to TNF-alpha-treated endothelial cells: evidence for an anti-inflammatory cascade mediated by the miR-221/222/AMPK/p38/NF-kappaB pathway. Sci Rep. 2017; 7: 44689. Liu J, Han X, Zhang T, Tian K, Li Z, Luo F. Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy, J Hematol Oncol. 2023; 16: 116. Liu Q, Wang SD, Cai L. Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage. J Diabetes Investig. 2014; 5: 623-34. Luo YD, Ma JJ, Lu WQ. The significance of mitochondrial dysfunction in cancer. Int J Mol Sci. 2020; 21: 5598. Madamanchi NR, Runge MS. Mitochondrial dysfunction in atherosclerosis. Circ Res. 2007; 100: 460-73. Mandl A, Pham LH, Toth K, Zambetti G, Erhardt P. Puma deletion delays cardiac dysfunction in murine heart failure models through attenuation of apoptosis. Circulation. 2011; 124: 31-U104. Martens S, McMahon HT. Mechanisms of membrane fusion: disparate players and common principles. Nat Rev Mol Cell Biol. 2008; 9: 543-56. Matsuda M, Shimomura I. Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord. 2014; 15: 1-10. Maulik SK, Kumar S. Oxidative stress and cardiac hypertrophy: a review. Toxicol Mech Methods. 2012; 22: 359-66. Mei Y, Thompson MD, Cohen RA, Tong X. Autophagy and oxidative stress in cardiovascular diseases. Biochim Biophys Acta. 2015; 1852: 243-51. Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH, Anderson GL, et al. Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med. 2007; 356: 447-58. Misra MK, Sarwat M, Bhakuni P, Tuteja R, Tuteja N. Oxidative stress and ischemic myocardial syndromes. Med Sci Monit. 2009; 15: Ra209-Ra19. Nethery RC, Josey K, Gandhi P, Kim JH, Visaria A, Bates B, et al. Air pollution and cardiovascular and thromboembolic events in older adults with high-risk conditions, Am J Epidemiol. 2023; 192: 1358-70. Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with crohn's disease. Gastroenterology. 2018; 154: 1334-42 e4. Plotnikov EY, Vasileva AK, Arkhangelskaya AA, Pevzner IB, Skulachev VP, Zorov DB. Interrelations of mitochondrial fragmentation and cell death under ischemia/reoxygenation and UV-irradiation: protective effects of SkQ1, lithium ions and insulin. FEBS Lett. 2008; 582: 3117-24. Pu CM, Liu CW, Liang CJ, Yen YH, Chen SH, Jiang-Shieh YF, et al. Adipose-derived stem cells protect skin flaps against ischemia/reperfusion injury via IL-6 expression. J Invest Dermatol. 2017; 137: 1353-62. Quiat D, Olson EN. MicroRNAs in cardiovascular disease: from pathogenesis to prevention and treatment. J Clin Invest. 2013; 123: 11-8. Quiles JM, Gustafsson ÅB. The role of mitochondrial fission in cardiovascular health and disease. Nat Rev Cardiol. 2022; 19: 723-36. Sacks FM, Lichtenstein AH, Wu JHY, Appel LJ, Creager MA, Kris-Etherton PM, et al. Dietary fats and cardiovascular disease a presidential advisory from the american heart association. Circulation. 2017; 136: e1-e23. Sagheer U, Al-Kindi S, Abohashem S, Phillips CT, Rana JS, Bhatnagar A, et al. Environmental pollution and cardiovascular disease: part 1 of 2: air pollution. JACC Adv. 2023; 3: 100805. Savini I, Catani MV, Evangelista D, Gasperi V, Avigliano L. Obesity-associated oxidative stress: strategies finalized to improve redox state. Int J Mol Sci. 2013; 14: 10497-538. Sawyer DB, Colucci WS. Mitochondrial oxidative stress in heart failure - "oxygen wastage" revisited. Circ Res. 2000; 86: 119-20. Scheffer DD, Garcia AA, Lee LC, Mochly-Rosen D, Ferreira JCB. Mitochondrial fusion, fission, and mitophagy in cardiac diseases: challenges and therapeutic opportunities. Antioxid Redox Signal. 2022; 36: 844-63. Sessa F, Salerno M, Esposito M, Cocimano G, Pomara C. miRNA dysregulation in cardiovascular diseases: current opinion and future perspectives. Int J Mol Sci. 2023; 24: 5196. Shah AS, Langrish JP, Nair H, McAllister DA, Hunter AL, Donaldson K, et al. Global association of air pollution and heart failure: a systematic review and meta-analysis. Lancet. 2013; 382: 1039-48. Shen X, Zheng SR, Metreveli NS, Epstein PN. Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes. 2006; 55: 798-805. Shin TH, Kim SG, Ji M, Kwon DH, Hwang JS, George NP, et al. Diesel-derived PM(2.5) induces impairment of cardiac movement followed by mitochondria dysfunction in cardiomyocytes. Front Endocrinol (Lausanne). 2022; 13: 999475. Shukla L, Yuan Y, Shayan R, Greening DW, Karnezis T. Fat Therapeutics: the clinical capacity of adipose-derived stem cells and exosomes for human disease and tissue regeneration. Front Pharmacol. 2020; 11: 158. Sun QH, Yue PB, Ying ZK, Cardounel AJ, Brook RD, Devlin R, et al. Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK. Arterioscler Thromb Vasc Biol. 2008; 28: 1760-6. Sung HC, Liu CW, Hsiao CY, Lin SR, Yu IS, Lin SW, et al. The effects of wild bitter gourd fruit extracts on ICAM-1 expression in pulmonary epithelial cells of C57BL/6J mice and microRNA-221/222 knockout mice: Involvement of the miR-221/-222/PI3K/AKT/NF-kappaB pathway. Phytomedicine. 2018; 42: 90-9. Tapp H, Hanley EN, Jr., Patt JC, Gruber HE. Adipose-derived stem cells: characterization and current application in orthopaedic tissue repair. Exp Biol Med (Maywood). 2009; 234: 1-9. Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013; 93: 359-404. Tokuyama T, Yanagi S. Role of mitochondrial dynamics in heart diseases. Genes (Basel). 2023; 14: 1876. Tsutsui H, Kinugawa S, Matsushima S. Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol. 2011; 301: H2181-H90. Vásquez-Trincado C, García-Carvajal I, Pennanen C, Parra V, Hill JA, Rothermel BA, et al. Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol. 2016; 594: 509-25. Wakabayashi J, Zhang ZY, Wakabayashi N, Tamura Y, Fukaya M, Kensler TW, et al. The dynamin-related GTPase drp1 is required for embryonic and brain development in mice. J Cell Biol. 2009; 186: 805-16. Wali JA, Jarzebska N, Raubenheimer D, Simpson SJ, Rodionov RN, O'Sullivan JF. Cardio-metabolic effects of high-fat diets and their underlying mechanisms-a narrative review. Nutrients. 2020; 12: 1505. Wang C, Tu Y, Yu Z, Lu R. PM2.5 and cardiovascular diseases in the elderly: an overview. Int J Environ Res Public Health. 2015; 12: 8187-97. Wang H, Peng X, Cao F, Wang Y, Shi H, Lin S, et al. Cardiotoxicity and mechanism of particulate matter 2.5 (PM2.5) exposure in offspring rats during pregnancy. Med Sci Monit. 2017; 23: 3890-6. Wasserman AH, Abolibdeh B, Hamdan R, Hong CC. Stem-cell derived exosomal microRNAs as biomarkers and therapeutics for pediatric cardiovascular disease. Curr Treat Options Cardiovasc Med. 2025; 27: 32. Wei CD, Li Y, Zheng HY, Tong YQ, Dai W. Palmitate induces H9c2 cell apoptosis by increasing reactive oxygen species generation and activation of the ERK1/2 signaling pathway. Mol Med Rep. 2013; 7: 855-61. Weichenthal S, Hoppin JA, Reeves F. Obesity and the cardiovascular health effects of fine particulate air pollution. Obesity (Silver Spring). 2014; 22: 1580-9. Wojciechowska A, Braniewska A, Kozar-Kaminska K. MicroRNA in cardiovascular biology and disease. Adv Clin Exp Med. 2017; 26: 865-74. World Health Organization. WHO global air quality guidelines: particulate matter (PM2.5 and PM10), ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide. Geneva: World Health Organization; 2021. Available from: https://www.who.int/publications/i/item/9789240034228 Wu KM, Hsu YM, Ying MC, Tsai FJ, Tsai CH, Chung JG, et al. High-density lipoprotein ameliorates palmitic acid-induced lipotoxicity and oxidative dysfunction in H9c2 cardiomyoblast cells via ROS suppression. Nutr Metab (Lond). 2019; 16: 36. Wu X, Yan F, Wang L, Sun G, Liu J, Qu M, et al. MicroRNA: another pharmacological avenue for colorectal cancer? Front Cell Dev Biol. 2020; 8: 812. Yang X, Li Y, Li Y, Ren X, Zhang X, Hu D, et al. Oxidative stress-mediated atherosclerosis: mechanisms and therapies, Front Physiol. 2017; 8: 600. Zhai X, Wang J, Sun J, Xin L. PM(2.5) induces inflammatory responses via oxidative stress-mediated mitophagy in human bronchial epithelial cells. Toxicol Res (Camb). 2022; 11: 195-205. Zhang CZ, Zhang JX, Zhang AL, Shi ZD, Han L, Jia ZF, et al. MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma, Mol Cancer. 2010; 9: 229. Zhang J, Liu Y, Chen Y, Yuan L, Liu H, Wang J, et al. Adipose-derived stem cells: current applications and future directions in the regeneration of multiple tissues. Stem Cells Int. 2020; 2020: 8810813. Zhang JJ, Wei Y, Fang Z. Ozone pollution: a major health hazard worldwide. Front Immunol. 2019; 10: 2518. Zhang J, Wang X, Vikash V, Ye Q, Wu D, Liu Y, et al. ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev. 2016; 2016: 4350965. Zhang Y, Xing Y, Jia L, Ji Y, Zhao B, Wen Y, et al. An in vitro comparative study of multisource derived human mesenchymal stem cells for bone tissue engineering. Stem Cells Dev. 2018; 27: 1634-45. Zhao L, Zhuang J, Wang Y, Zhou D, Zhao D, Zhu S, et al. Propofol ameliorates H9c2 cells apoptosis induced by oxygen glucose deprivation and reperfusion injury via inhibiting high levels of mitochondrial fusion and fission. Front Pharmacol. 2019; 10: 61. Zhou B, Tian R. Mitochondrial dysfunction in pathophysiology of heart failure. J Clin Invest. 2018; 128: 3716-26. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99371 | - |
| dc.description.abstract | 空氣污染與肥胖為心血管疾病(cardiovascular diseases, CVDs)的重要危險因子。流行病學研究指出，空氣污染可加劇肥胖所誘導的心臟損傷。脂肪間質幹細胞(adipose-derived stem cells, ADSCs)的旁分泌作用已被證明可以減輕心臟損傷，然而，其對空氣污染與肥胖共同誘導之心肌細胞凋亡的影響及其潛在機制仍未明確。本研究利用棕櫚酸(palmitic acid, PA)與高脂飲食(high-fat diet, HFD)誘導肥胖模型，並以懸浮微粒(particulate matter, PM)模擬空氣污染，探討ADSC條件培養液(ADSC-conditioned medium, ADSC-CM)對PA+PM處理後的H9c2細胞及HFD+PM處理小鼠心肌細胞之凋亡效應及其相關分子機轉。
透過Western blot分析檢測凋亡相關蛋白表現，研究結果顯示，在PA+PM處理之H9c2細胞與HFD+PM處理之小鼠心肌細胞中，促凋亡蛋白PUMA與cleaved Caspase-3表現顯著上升，抗凋亡蛋白Bcl-2表現則下降。然而，ADSC-CM處理可有效降低PUMA與cleaved Caspase-3的表現，同時增加Bcl-2表現。另外，TUNEL與Annexin V/PI染色結果進一步證實，ADSC-CM顯著減少PA+PM與HFD+PM誘導之心肌細胞凋亡。RT-qPCR結果顯示，PA+PM與HFD+PM處理顯著降低miR221/222的表現，而ADSC-CM處理則可回復其表現。進一步使用miR221/222基因剔除(knockout, KO)與轉基因(transgenic, TG)小鼠模型，證實ADSC-CM中的miR221/222可緩解HFD+PM誘導之心肌細胞凋亡。此外，本研究也發現PA+PM處理會增加細胞內活性氧(reactive oxygen species, ROS)生成，進而誘發粒線體分裂，促進細胞凋亡；然而，ADSC-CM可有效抑制ROS產生並調控粒線體分裂，進而減緩細胞凋亡現象。綜合以上結果，ADSC-CM可透過正向調控miR221/222表現與降低ROS產生，進一步調控粒線體功能，從而減輕PA+PM誘導之心肌細胞凋亡，展現其潛在的心肌保護效果。 | zh_TW |
| dc.description.abstract | Air pollution and obesity are critical risk factors for cardiovascular diseases (CVDs), and epidemiological studies have shown that air pollution exacerbates obesity-induced cardiac damage. Adipose-derived stem cells (ADSCs) exert paracrine effects that have been reported to attenuate cardiac injury; however, the effects of ADSCs in preventing cardiomyocyte apoptosis induced by obesity and air pollution, as well as the underlying mechanisms, remain unclear. In this study, palmitic acid (PA) and high-fat diet (HFD) were used to induce obesity, and particulate matter (PM) was applied to simulate air pollution exposure. We studied the effect of adipose-derived stem cell-conditioned medium (ADSC-CM) on apoptosis of PA+PM-treated H9c2 cells and HFD+PM-treated mouse cardiomyocytes and its related mechanisms. Western blot analysis was conducted to assess the expression of apoptosis-related proteins. The results showed that the apoptosis-related proteins PUMA and cleaved Caspase-3 were significantly upregulated in PA+PM-treated H9c2 cells and HFD+PM-treated mouse cardiomyocytes, while the anti-apoptosis-related protein Bcl-2 was markedly decreased. Notably, treatment with ADSC-CM effectively reduced the protein expression of PUMA and cleaved Caspase-3 expression, while increasing that of Bcl-2. TUNEL assay and Annexin V/PI staining further confirmed that ADSC-CM significantly attenuated PA+PM- and HFD+PM-induced cardiomyocyte apoptosis. RT-qPCR detection found that PA+PM and HFD+PM significantly reduced miR221/222 levels, while ADSC-CM treatment increased miR221/222 levels. Furthermore, knockout (KO) and transgenic (TG) mice were used to demonstrate that miR221/222 in ADSC-CM ameliorated cardiac apoptosis induced by HFD+PM treatment. In addition, PA+PM treatment increased the production of reactive oxygen species (ROS), which triggered mitochondrial fission and contributed to apoptosis. However, ADSC-CM could effectively reduce ROS and regulate mitochondrial fission, alleviating cellular apoptosis. In conclusion, these findings demonstrated that ADSC-CM attenuates PA+PM-induced cardiomyocyte apoptosis through the modulation of miR221/222 and the suppression of ROS. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-09T16:11:17Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-09T16:11:17Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 (Acknowledgements) I
中文摘要 II Abstract III List of figures X List of tables XII 1. Introduction 1 1.1. The cardiac structure, function, and cardiovascular diseases (CVDs) 1 1.2. Obesity and its role in cardiovascular injury 3 1.3. Particulate matter (PM) and its role in cardiovascular injury 5 1.4. Adipose-derived stem cells (ADSCs) and their secretome as cardioprotective agents 8 1.5. The regulatory role of miR221/222 in cardiovascular pathophysiology 9 1.6. ROS, mitochondrial dysfunction, and cardiomyocyte injury 11 1.7. Rationale for the Study 13 2. Materials and Methods 15 2.1. Cell culture 15 2.2. PM preparation 15 2.3. ADSC conditioned medium preparation 16 2.4. MTT assay 16 2.5. Western blot analysis 16 2.6. TUNEL assay 17 2.7. Annexin V-FITC/propidium iodide (PI) staining 18 2.8. Real-time PCR 18 2.9. Transient Transfection 19 2.10. Animal experimentation 19 2.11. Assessment of cardiac function 20 2.12. Histopathological staining 21 2.13. MitoSOX Red staining 21 2.14. JC-1 staining 22 2.15. ATP measurement 22 2.16. Assessment of mitochondrial length 23 2.17. Statistical analysis 23 3. Results 26 3.1. PA and PM reduce cell viability and promote apoptosis-related protein expression in H9c2 cardiomyocytes 26 3.2. Combined PA and PM treatment synergistically enhances apoptosis-related protein expression in H9c2 cardiomyocytes 27 3.3. ADSC-CM attenuates PA+PM-induced apoptosis in H9c2 cardiomyocytes 27 3.4. MiR221/222 attenuate PA+PM-induced apoptosis-related protein expression in H9c2 cardiomyocytes 28 3.5. MiR221/222 in ADSC-CM attenuates PA+PM-induced apoptosis-related protein expression in H9c2 cardiomyocytes 29 3.6. MiR221/222 are essential mediators of the anti-apoptotic effect of ADSC-CM 30 3.7. ADSC-CM improves cardiac function in HFD+PM-treated B6 and KO mice 31 3.8. ADSC-CM reduces cardiac apoptosis and PUMA expression in HFD+PM-treated hearts 32 3.9. MiR221/222 TG mice mitigates HFD+PM-induced cardiac injury 33 3.10. MiR221/222 TG mice presented fewer apoptotic cells under HFD and PM conditions 35 3.11. ADSC-CM attenuated PA+PM-induced mitochondrial ROS (mROS) production in H9c2 cardiomyocytes 36 3.12. ADSC-CM reduces PA+PM-induced ROS production through a mechanism independent of miR221/222 37 3.13. ADSC-CM attenuates PA+PM-induced H9c2 cell apoptosis by upregulating SOD2 expression 38 3.14. ADSC-CM reduced PA+PM-induced mitochondrial fission in H9c2 cardiomyocytes 38 3.15. ROS triggers mitochondrial dysfunction and fission, leading to apoptosis in H9c2 cardiomyocytes 39 3.16. ADSC-CM reduces ROS and mitochondrial dysfunction through a miR221/222-independent pathway 40 4. Discussion 42 5. Concussion 55 References 57 Figures and figure legends 73 List of figures Figure 1: Effects of PA and PM on cell viability and apoptosis-related protein expression in H9c2 cells 73 Figure 2: Combined effects of PA and PM on cell viability and apoptosis-related protein expression in H9c2 cells 74 Figure 3: Effects of ADSC-CM on PA+PM-induced apoptosis in H9c2 cells 75 Figure 4: Effects of miR221/222 on PA+PM-induced apoptosis in H9c2 cells 77 Figure 5: Effects of miR221/222 inhibition on ADSC-CM-mediated protection against PA+PM-induced apoptosis-related protein expression in H9c2 cells 79 Figure 6: Effects of ADSC-CM lacking miR221/222 on PA+PM-induced apoptosis in H9c2 cells 80 Figure 7: Effects of ADSC-CM on cardiac function in HFD+PM-exposed B6 and KO mice 81 Figure 8: Histological and molecular analysis of cardiac apoptosis in HFD+PM-treated B6 and KO mice 83 Figure 9: Effects of ADSC-CM on cardiac function in HFD+PM-exposed TG mice 85 Figure 10: Histological and molecular analysis of cardiac apoptosis in HFD+PM-treated TG mice 87 Figure 11: Effects of MitoQ and ADSC-CM on mitochondrial ROS accumulation and apoptosis in PA+PM-treated H9c2 cells 88 Figure 12: Effects of miR221/222 mimics on mitochondrial ROS production in PA+PM-treated H9c2 cells 90 Figure 13: Effects of ADSC-CM on the expression of SOD1, SOD2, and SOD3 in PA+PM-induced H9c2 cells 92 Figure 14: Effects of ADSC-CM on mitochondrial fission of H9c2 cells induced by PA and PM 94 Figure 15: Effects of MitoQ, H₂O₂, and Mdivi-1 on ROS-induced mitochondrial fission 96 Figure 16: Effects of miR221/222 on ROS-mediated mitochondrial injury and antioxidant response in H9c2 cells 98 Figure 17: A graphical abstract summarizing the study findings 99 List of tables Table 1 Antibodies used in immunoblotting studies. 24 Table 2 Antibodies used in immunohistochemistry studies 25 | - |
| dc.language.iso | en | - |
| dc.subject | 懸浮微粒(PM) | zh_TW |
| dc.subject | 棕櫚酸(PA) | zh_TW |
| dc.subject | 高脂飲食(HFD) | zh_TW |
| dc.subject | ADSC-CM | zh_TW |
| dc.subject | miR221/222 | zh_TW |
| dc.subject | 活性氧(ROS) | zh_TW |
| dc.subject | 粒線體分裂 | zh_TW |
| dc.subject | Palmitic acid (PA) | en |
| dc.subject | Mitochondrial fission | en |
| dc.subject | Reactive oxygen species (ROS) | en |
| dc.subject | miR221/222 | en |
| dc.subject | ADSC-CM | en |
| dc.subject | High-fat diet (HFD) | en |
| dc.subject | Particulate matter (PM) | en |
| dc.title | 研究脂肪幹細胞條件培養基對暴露於懸浮微粒與高脂肪飲食的心肌細胞之影響及相關機轉 | zh_TW |
| dc.title | To study the effects of conditioned medium from adipose-derived stem cells on cardiomyocytes exposed to particulate matter and high-fat diet and related mechanisms | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 李江文;蒲啟明;陳瀅;王淑慧 | zh_TW |
| dc.contributor.oralexamcommittee | Chiang-Wen Lee;Chi-Ming Pu;Ying Chen;Shu-Huei Wang | en |
| dc.subject.keyword | 懸浮微粒(PM),棕櫚酸(PA),高脂飲食(HFD),ADSC-CM,miR221/222,活性氧(ROS),粒線體分裂, | zh_TW |
| dc.subject.keyword | Particulate matter (PM),Palmitic acid (PA),High-fat diet (HFD),ADSC-CM,miR221/222,Reactive oxygen species (ROS),Mitochondrial fission, | en |
| dc.relation.page | 99 | - |
| dc.identifier.doi | 10.6342/NTU202501905 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-07-17 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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