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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張以承 | zh_TW |
| dc.contributor.advisor | Yi-Cheng Chang | en |
| dc.contributor.author | 邱楚璿 | zh_TW |
| dc.contributor.author | Chu-Hsuan Chiu | en |
| dc.date.accessioned | 2023-09-20T16:17:23Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2023-09-20 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-06-17 | - |
| dc.identifier.citation | 1. Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers. 2019;5(1):56. Published 2019 Aug 16. doi:10.1038/s41572-019-0106-z
2. Matsunaga H, Ito K, Akiyama M, et al. Transethnic Meta-Analysis of Genome-Wide Association Studies Identifies Three New Loci and Characterizes Population-Specific Differences for Coronary Artery Disease. Circ Genom Precis Med. 2020;13(3):e002670. doi:10.1161/CIRCGEN.119.002670 3. McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316(5830):1488-1491. doi:10.1126/science.1142447 4. Samani NJ, Erdmann J, Hall AS, et al. Genome wide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443-453. doi:10.1056/NEJMoa072366 5. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661-678. doi:10.1038/nature05911 6. Coronary Artery Disease Consortium, Samani NJ, Deloukas P, et al. Large scale association analysis of novel genetic loci for coronary artery disease. Arterioscler Thromb Vasc Biol. 2009;29(5):774-780. doi:10.1161/ATVBAHA.108.181388 7. Erdmann J, Grosshennig A, Braund PS, et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nat Genet. 2009;41(3):280-282. doi:10.1038/ng.307 8. Nikpay M, Goel A, Won HH, et al. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015;47(10):1121-1130. doi:10.1038/ng.3396 9. Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316(5830):1491-1493. doi:10.1126/science.1142842 10. Trégouët DA, König IR, Erdmann J, et al. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat Genet. 2009;41(3):283-285. doi:10.1038/ng.314 11. GBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [published correction appears in Lancet. 2019 Jan 12;393(10167):132] [published correction appears in Lancet. 2019 Jun 22;393(10190):e44].Lancet.2018;392(10159):1923-1994.doi:10.1016/S0140-6736(18)32225-6 12. Mills KT, Bundy JD, Kelly TN, et al. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation. 2016;134(6):441-450. doi:10.1161/CIRCULATIONAHA.115.018912 13. GBD 2013 Risk Factors Collaborators, Forouzanfar MH, Alexander L, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(10010):2287-2323. doi:10.1016/S0140-6736(15)00128-2 14. Ibrahim MM, Damasceno A. Hypertension in developing countries. Lancet. 2012;380(9841):611-619. doi:10.1016/S0140-6736(12)60861-7 15. Liu J, Zhou Y, Liu Y, et al. (Pro)renin receptor regulates lung development via the Wnt/β-catenin signaling pathway. Am J Physiol Lung Cell Mol Physiol. 2019;317(2):L202-L211. doi:10.1152/ajplung.00295.2018 16. Santos RAS, Oudit GY, Verano-Braga T, Canta G, Steckelings UM, Bader M. The renin-angiotensin system: going beyond the classical paradigms. Am J Physiol Heart Circ Physiol. 2019;316(5):H958-H970. doi:10.1152/ajpheart.00723.2018 17. Nehme A, Zouein FA, Zayeri ZD, Zibara K. An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology. J Cardiovasc Dev Dis. 2019;6(2):14. Published 2019 Mar 29. doi:10.3390/jcdd6020014 18. Sinn PL, Zhang X, Sigmund CD. JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter. Am J Physiol. 1999;277(4):F634-F642. doi:10.1152/ajprenal.1999.277.4.F634 19. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. In: StatPearls. Treasure Island (FL): StatPearls Publishing; June 18, 2022. 20. Wu C, Lu H, Cassis LA, Daugherty A. Molecular and Pathophysiological Features of Angiotensinogen: A Mini Review. N Am J Med Sci (Boston). 2011;4(4):183-190. doi:10.7156/v4i4p183 21. Lu H, Cassis LA, Kooi CW, Daugherty A. Structure and functions of angiotensinogen [published correction appears in Hypertens Res. 2016 Nov;39(11):827]. Hypertens Res. 2016;39(7):492-500. doi:10.1038/hr.2016.17 22. Fukamizu A, Sugimura K, Takimoto E, et al. Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes. J Biol Chem. 1993;268(16):11617-11621. 23. Hatae T, Takimoto E, Murakami K, Fukamizu A. Comparative studies on species-specific reactivity between renin and angiotensinogen. Mol Cell Biochem. 1994;131(1):43-47. doi:10.1007/BF01075723 24. HELMER OM. Differentiation between two forms of angiotonin by means of spirally cut strips of rabbit aorta. Am J Physiol. 1957;188(3):571-577. doi:10.1152/ajplegacy.1957.188.3.571 25. Yang HY, Erdös EG, Levin Y. A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochim Biophys Acta. 1970;214(2):374-376. doi:10.1016/0005-2795(70)90017-6 26. Erdös EG. Conversion of angiotensin I to angiotensin II. Am J Med. 1976;60(6):749-759. doi:10.1016/0002-9343(76)90889-5 27. Skidgel RA, Erdös EG. Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies. Peptides. 2004;25(3):521-525. doi:10.1016/j.peptides.2003.12.010 28. Yoshida T, Nosaka S. Some characteristics of a peptidyl dipeptidase (kininase II) from rat CSF: differential effects of NaCl on the sequential degradation steps of bradykinin. J Neurochem. 1990;55(6):1861-1869. doi:10.1111/j.1471-4159.1990.tb05769.x 29. Abadir PM, Foster DB, Crow M, et al. Identification and characterization of a functional mitochondrial angiotensin system. Proc Natl Acad Sci U S A. 2011;108(36):14849-14854. doi:10.1073/pnas.1101507108 30. Adiarto S, Heiden S, Vignon-Zellweger N, et al. ET-1 from endothelial cells is required for complete angiotensin II-induced cardiac fibrosis and hypertrophy. Life Sci. 2012;91(13-14):651-657. doi:10.1016/j.lfs.2012.02.006 31. Barhoumi T, Kasal DA, Li MW, et al. T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011;57(3):469-476. doi:10.1161/HYPERTENSIONAHA.110.162941 32. Bendall JK, Cave AC, Heymes C, Gall N, Shah AM. Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation. 2002;105(3):293-296. doi:10.1161/hc0302.103712 33. Santos RAS, Sampaio WO, Alzamora AC, et al. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiol Rev. 2018;98(1):505-553. doi:10.1152/physrev.00023.2016 34. Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling M. Multiple actions of steroid hormones--a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52(4):513-556. 35. Harvey BJ, Condliffe S, Doolan CM. Sex and salt hormones: rapid effects in epithelia. News Physiol Sci. 2001;16:174-177. doi:10.1152/physiologyonline.2001.16.4.174 36. Náray-Fejes-Tóth A, Fejes-Tóth G. The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel. Kidney Int. 2000;57(4):1290-1294. doi:10.1046/j.1523-1755.2000.00964.x 37. Verrey F. Early aldosterone action: toward filling the gap between transcription and transport. Am J Physiol. 1999;277(3):F319-F327. doi:10.1152/ajprenal.1999.277.3.F319 38. Booth RE, Johnson JP, Stockand JD. Aldosterone. Adv Physiol Educ. 2002;26(1-4):8-20. doi:10.1152/advan.00051.2001 39. Kim GH, Masilamani S, Turner R, Mitchell C, Wade JB, Knepper MA. The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein. Proc Natl Acad Sci U S A. 1998;95(24):14552-14557. doi:10.1073/pnas.95.24.14552 40. Cho JH, Musch MW, Bookstein CM, McSwine RL, Rabenau K, Chang EB. Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3 expression of the proximal colon. Am J Physiol. 1998;274(3):C586-C594. doi:10.1152/ajpcell.1998.274.3.C586 41. Kurtz A. Control of renin synthesis and secretion. Am J Hypertens. 2012;25(8):839-847. doi:10.1038/ajh.2011.246 42. Persson PB. Renin: origin, secretion and synthesis. J Physiol. 2003;552(Pt 3):667-671. doi:10.1113/jphysiol.2003.049890 43. Cholewa BC, Mattson DL. Role of the renin-angiotensin system during alterations of sodium intake in conscious mice. Am J Physiol Regul Integr Comp Physiol. 2001;281(3):R987-R993. doi:10.1152/ajpregu.2001.281.3.R987 44. Peters J, Clausmeyer S. Intracellular sorting of renin: cell type specific differences and their consequences. J Mol Cell Cardiol. 2002;34(12):1561-1568. doi:10.1006/jmcc.2002.2079 45. Clausmeyer S, Stürzebecher R, Peters J. An alternative transcript of the rat renin gene can result in a truncated prorenin that is transported into adrenal mitochondria. Circ Res. 1999;84(3):337-344. doi:10.1161/01.res.84.3.337 46. Wanka H, Kessler N, Ellmer J, et al. Cytosolic renin is targeted to mitochondria and induces apoptosis in H9c2 rat cardiomyoblasts. J Cell Mol Med. 2009;13(9A):2926-2937. doi:10.1111/j.1582-4934.2008.00448.x 47. Peters J, Wanka H, Peters B, Hoffmann S. A renin transcript lacking exon 1 encodes for a non-secretory intracellular renin that increases aldosterone production in transgenic rats. J Cell Mol Med. 2008;12(4):1229-1237. doi:10.1111/j.1582-4934.2008.00132.x 48. De Mello WC, Frohlich ED. On the local cardiac renin angiotensin system. Basic and clinical implications. Peptides. 2011;32(8):1774-1779. doi:10.1016/j.peptides.2011.06.018 49. Pan L, Gross KW. Transcriptional regulation of renin: an update. Hypertension. 2005;45(1):3-8. doi:10.1161/01.HYP.0000149717.55920.45 50. Gomez RA, Pentz ES, Jin X, Cordaillat M, Sequeira Lopez ML. CBP and p300 are essential for renin cell identity and morphological integrity of the kidney. Am J Physiol Heart Circ Physiol. 2009;296(5):H1255-H1262. doi:10.1152/ajpheart.01266.2008 51. Desch M, Schreiber A, Schweda F, et al. Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells. Hypertension. 2010;55(3):660-666. doi:10.1161/HYPERTENSIONAHA.109.138800 52. Yuan W, Pan W, Kong J, et al. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem. 2007;282(41):29821-29830. doi:10.1074/jbc.M705495200 53. Todorov VT, Völkl S, Müller M, et al. Tumor necrosis factor-alpha activates NFkappaB to inhibit renin transcription by targeting cAMP-responsive element. J Biol Chem. 2004;279(2):1458-1467. doi:10.1074/jbc.M308697200 54. Pratt RE, Carleton JE, Richie JP, Heusser C, Dzau VJ. Human renin biosynthesis and secretion in normal and ischemic kidneys. Proc Natl Acad Sci U S A. 1987;84(22):7837-7840. doi:10.1073/pnas.84.22.7837 55. Danser AH, Deinum J. Renin, prorenin and the putative (pro)renin receptor. Hypertension. 2005;46(5):1069-1076. doi:10.1161/01.HYP.0000186329.92187.2e 56. Nguyen G, Muller DN. The biology of the (pro)renin receptor. J Am Soc Nephrol. 2010;21(1):18-23. doi:10.1681/ASN.2009030300 57. Brakch N, Allemandou F, Keller I, Nussberger J. The renin prosequence enhances constitutive secretion of renin and optimizes renin activity. Curr Neurovasc Res. 2011;8(2):121-130. doi:10.2174/156720211795495367 58. Sequeira Lopez ML, Gomez RA. Novel mechanisms for the control of renin synthesis and release. Curr Hypertens Rep. 2010;12(1):26-32. doi:10.1007/s11906-009-0080-z 59. Torretti J. Sympathetic control of renin release. Annu Rev Pharmacol Toxicol. 1982;22:167-192. doi:10.1146/annurev.pa.22.040182.001123 60. Persson AE, Ollerstam A, Liu R, Brown R. Mechanisms for macula densa cell release of renin. Acta Physiol Scand. 2004;181(4):471-474. doi:10.1111/j.1365-201X.2004.01320.x 61. Watanabe H, Belyea BC, Paxton RL, et al. Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis. Circ Res. 2021;129(2):262-276. doi:10.1161/CIRCRESAHA.120.318711 62. Feldman RD, Gros R. New insights into the regulation of cAMP synthesis beyond GPCR/G protein activation: implications in cardiovascular regulation. Life Sci. 2007;81(4):267-271. doi:10.1016/j.lfs.2007.05.015 63. Beierwaltes WH. The role of calcium in the regulation of renin secretion. Am J Physiol Renal Physiol. 2010;298(1):F1-F11. doi:10.1152/ajprenal.00143.2009 64. Sousa AG, Cabral JV, El-Feghaly WB, de Sousa LS, Nunes AB. Hyporeninemic hypoaldosteronism and diabetes mellitus: Pathophysiology assumptions, clinical aspects and implications for management. World J Diabetes. 2016;7(5):101-111. doi:10.4239/wjd.v7.i5.101 65. Chelaghma N, Oyibo SO. Hyporeninemic hypoaldosteronism in a patient with diabetes mellitus: an unforgettable case report. Int Med Case Rep J. 2018;11:69-72. Published 2018 Apr 3. doi:10.2147/IMCRJ.S158628 66. Grande Villoria J, Macias Nunez JF, Miralles JM, De Castro del Pozo S, Tabernero Romo JM. Hyporeninemic hypoaldosteronism in diabetic patients with chronic renal failure. Am J Nephrol. 1988;8(2):127-137. doi:10.1159/000167571 67. DeFronzo RA. Hyperkalemia and hyporeninemic hypoaldosteronism. Kidney Int. 1980;17(1):118-134. doi:10.1038/ki.1980.14 68. Tan SY, Burton M. Hyporeninemic hypoaldosteronism. An overlooked cause of hyperkalemia. Arch Intern Med. 1981;141(1):30-33. doi:10.1001/archinte.141.1.30 69. Hollander-Rodriguez JC, Calvert JF Jr. Hyperkalemia. Am Fam Physician. 2006;73(2):283-290. 70. Te Dorsthorst RPM, Hendrikse J, Vervoorn MT, van Weperen VYH, van der Heyden MAG. Review of case reports on hyperkalemia induced by dietary intake: not restricted to chronic kidney disease patients. Eur J Clin Nutr. 2019;73(1):38-45. doi:10.1038/s41430-018-0154-6 71. Palmer BF, Clegg DJ. Physiology and Pathophysiology of Potassium Homeostasis: Core Curriculum 2019. Am J Kidney Dis. 2019;74(5):682-695. doi:10.1053/j.ajkd.2019.03.427 72. Watanabe T, Nitta K. Transient hyporeninemic hypoaldosteronism in acute glomerulonephritis. Pediatr Nephrol. 2002;17(11):959-963. doi:10.1007/s00467-002-0984-1 73. Malik WA, Labib MH, Irfan H. Hyporeninaemic hypoaldosteronism and systemic amyloidosis. Ann Clin Biochem. 1995;32 ( Pt 6):593-594. doi:10.1177/000456329503200614 74. Schnermann J. Juxtaglomerular cell complex in the regulation of renal salt excretion. Am J Physiol. 1998;274(2):R263-R279. doi:10.1152/ajpregu.1998.274.2.R263 75. Alhenc-Gelas F. A new channel for the control of renin secretion in juxtaglomerular cells. Kidney Int. 2020;98(3):543-545. doi:10.1016/j.kint.2020.05.031 76. Wanker EE, Sun Y, Savitz AJ, Meyer DI. Functional characterization of the 180-kD ribosome receptor in vivo. J Cell Biol. 1995;130(1):29-39. doi:10.1083/jcb.130.1.29 77. Benyamini P, Webster P, Meyer DI. KD of p180 eliminates the terminal differentiation of a secretory cell line. Mol Biol Cell. 2009;20(2):732-744. doi:10.1091/mbc.e08-07-0682 78. Savitz AJ, Meyer DI. 180-kD ribosome receptor is essential for both ribosome binding and protein translocation. J Cell Biol. 1993;120(4):853-863. doi:10.1083/jcb.120.4.853 79. Cui XA, Zhang H, Palazzo AF. p180 promotes the ribosome-independent localization of a subset of mRNA to the endoplasmic reticulum. PLoS Biol. 2012;10(5):e1001336. doi:10.1371/journal.pbio.1001336 80. Ueno T, Kaneko K, Sata T, Hattori S, Ogawa-Goto K. Regulation of polysome assembly on the endoplasmic reticulum by a coiled-coil protein, p180. Nucleic Acids Res. 2012;40(7):3006-3017. doi:10.1093/nar/gkr1197 81. Ogawa-Goto K, Tanaka K, Ueno T, et al. p180 is involved in the interaction between the endoplasmic reticulum and microtubules through a novel microtubule-binding and bundling domain. Mol Biol Cell. 2007;18(10):3741-3751. doi:10.1091/mbc.e06-12-1125 82. Bai JZ, Leung E, Holloway H, Krissansen GW. Alternatively spliced forms of the P180 ribosome receptor differ in their ability to induce the proliferation of rough endoplasmic reticulum. Cell Biol Int. 2008;32(5):473-483. doi:10.1016/j.cellbi.2007.10.002 83. Becker F, Block-Alper L, Nakamura G, Harada J, Wittrup KD, Meyer DI. Expression of the 180-kD ribosome receptor induces membrane proliferation and increased secretory activity in yeast. J Cell Biol. 1999;146(2):273-284. doi:10.1083/jcb.146.2.273 84. Ueno T, Tanaka K, Kaneko K, et al. Enhancement of procollagen biosynthesis by p180 through augmented ribosome association on the endoplasmic reticulum in response to stimulated secretion. J Biol Chem. 2010;285(39):29941-29950. doi:10.1074/jbc.M109.094607 85. Yasuno K, Bakırcıoğlu M, Low SK, et al. Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk. Proc Natl Acad Sci U S A. 2011;108(49):19707-19712. doi:10.1073/pnas.1117137108 86. Vuckovic D, Bao EL, Akbari P, et al. The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell. 2020;182(5):1214-1231.e11. doi:10.1016/j.cell.2020.08.008 87. van der Harst P, Verweij N. Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease. Circ Res. 2018;122(3):433-443. doi:10.1161/CIRCRESAHA.117.312086 88. Anastasia I, Ilacqua N, Raimondi A, et al. Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis. Cell Rep. 2021;34(11):108873. doi:10.1016/j.celrep.2021.108873 89. Boini KM, Nammi S, Grahammer F, Osswald H, Kuhl D, Lang F. Role of serum- and glucocorticoid-inducible kinase SGK1 in glucocorticoid regulation of renal electrolyte excretion and blood pressure. Kidney Blood Press Res. 2008;31(4):280-289. doi:10.1159/000151666 90. Iravanian S, Dudley SC Jr. The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias [published correction appears in Heart Rhythm. 2008 Oct;5(10):1499]. Heart Rhythm. 2008;5(6 Suppl):S12-S17. doi:10.1016/j.hrthm.2008.02.025 91. Chuang LM, Chiu YF, Sheu WH, et al. Biethnic comparisons of autosomal genomic scan for loci linked to plasma adiponectin in populations of Chinese and Japanese origin. J Clin Endocrinol Metab. 2004;89(11):5772-5778. doi:10.1210/jc.2004-0640 92. Lange C, Silverman EK, Xu X, Weiss ST, Laird NM. A multivariate family-based association test using generalized estimating equations: FBAT-GEE. Biostatistics. 2003;4(2):195-206. doi:10.1093/biostatistics/4.2.195 93. Liu P, Jenkins NA, Copeland NG. A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res. 2003;13(3):476-484. doi:10.1101/gr.749203 94. Huang CH, Shih YY, Siow TY, et al. Temporal assessment of vascular reactivity and functionality using MRI during postischemic proangiogenenic vascular remodeling. Magn Reson Imaging. 2015;33(7):903-910. doi:10.1016/j.mri.2015.04.009 95. Hsiao HY, Chen YC, Huang CH, et al. Aberrant astrocytes impair vascular reactivity in Huntington disease. Ann Neurol. 2015;78(2):178-192. doi:10.1002/ana.24428 96. Cesarovic N, Jirkof P, Rettich A, Arras M. Implantation of radiotelemetry transmitters yielding data on ECG, heart rate, core body temperature and activity in free-moving laboratory mice. J Vis Exp. 2011;(57):3260. Published 2011 Nov 21. doi:10.3791/3260 97. Shendre A, Irvin MR, Wiener H, et al. Local Ancestry and Clinical Cardiovascular Events Among African Americans From the Atherosclerosis Risk in Communities Study. J Am Heart Assoc. 2017;6(4):e004739. Published 2017 Apr 10. doi:10.1161/JAHA.116.004739 98. Richardson TG, Sanderson E, Palmer TM, et al. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med. 2020;17(3):e1003062. Published 2020 Mar 23. doi:10.1371/journal.pmed.1003062 99. Backman JD, Li AH, Marcketta A, et al. Exome sequencing and analysis of 454,787 UK Biobank participants. Nature. 2021;599(7886):628-634. doi:10.1038/s41586-021-04103-z 100. Paquette M, Chong M, Thériault S, Dufour R, Paré G, Baass A. Polygenic risk score predicts prevalence of cardiovascular disease in patients with familial hypercholesterolemia. J Clin Lipidol. 2017;11(3):725-732.e5. doi:10.1016/j.jacl.2017.03.019 101. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med. 2001;345(20):1473-1482. doi:10.1056/NEJMra000650 102. Weiner ID, Wingo CS. Hyperkalemia: a potential silent killer. J Am Soc Nephrol. 1998;9(8):1535-1543. doi:10.1681/ASN.V981535 103. Webster A, Brady W, Morris F. Recognising signs of danger: ECG changes resulting from an abnormal serum potassium concentration. Emerg Med J. 2002;19(1):74-77. doi:10.1136/emj.19.1.74 104. Mattu A, Brady WJ, Robinson DA. Electrocardiographic manifestations of hyperkalemia. Am J Emerg Med. 2000;18(6):721-729. doi:10.1053/ajem.2000.7344 105. Littmann L, Gibbs MA. Electrocardiographic manifestations of severe hyperkalemia. J Electrocardiol. 2018;51(5):814-817. doi:10.1016/j.jelectrocard.2018.06.018 106. Rastegar A, Soleimani M. Hypokalaemia and hyperkalaemia [published correction appears in Postgrad Med J 2002 Feb;78(916):126. Rastergar A [corrected to Rastegar A]]. Postgrad Med J. 2001;77(914):759-764. doi:10.1136/pmj.77.914.759 107. Shinagawa T, Do YS, Baxter J, Hsueh WA. Purification and characterization of human truncated prorenin. Biochemistry. 1992;31(10):2758-2764. doi:10.1021/bi00125a016 108. Hirose S, Kim S, Miyazaki H, Park YS, Murakami K. In vitro biosynthesis of human renin and identification of plasma inactive renin as an activation intermediate. J Biol Chem. 1985;260(30):16400-16405. 109. Lang JA, Yang G, Kern JA, Sigmund CD. Endogenous human renin expression and promoter activity in CALU-6, a pulmonary carcinoma cell line. Hypertension. 1995;25(4 Pt 2):704-710. doi:10.1161/01.hyp.25.4.704 110. Schambelan M, Sebastian A, Biglieri EG. Prevalence, pathogenesis, and functional significance of aldosterone deficiency in hyperkalemic patients with chronic renal insufficiency. Kidney Int. 1980;17(1):89-101. doi:10.1038/ki.1980.11 111. deLeiva A, Christlieb AR, Melby JC, et al. Big renin and biosynthetic defect of aldosterone in diabetes mellitus. N Engl J Med. 1976;295(12):639-643. doi:10.1056/NEJM197609162951203 112. Ranade K, Wu KD, Risch N, et al. Genetic variation in aldosterone synthase predicts plasma glucose levels. Proc Natl Acad Sci U S A. 2001;98(23):13219-13224. doi:10.1073/pnas.221467098 113. Chiu CH, Hsuan CF, Lin SH, et al. ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking. J Biomed Sci. 2023;30(1):13. Published 2023 Feb 19. doi:10.1186/s12929-023-00905-7 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89766 | - |
| dc.description.abstract | RRBP1，又被稱為p180，是一種與內質網核糖體結合的蛋白。許多全基因組關聯分析的研究指出，RRBP1基因的變異與動脈硬化心血管疾病以及血液中的血脂蛋白含量有高度相關性。然而，關於RRBP1在調控心血管疾病中最重要的因素之一──「血壓」的角色，目前尚未被廣泛探討。本研究的主要目的在於釐清RRBP1在調控血壓以及在心血管生理上所扮演的角色。
首先，我們利用史丹佛亞洲及太平洋高血壓及胰島素阻抗計畫（Stanford Asia-Pacific Program for Hypertension and Insulin Resistance）中的世代研究資料庫，透過全基因組連鎖分析，發現RRBP1的基因變異與血壓有高度相關性。此外，我們進一步進行了Rrbp1基因剔除小鼠的實驗，結果顯示這些小鼠表現出低血壓並出現早發型未預期的猝死。透過血液生化檢測，我們發現Rrbp1基因剔除小鼠患有低腎素型低醛固酮血症（hyporeninemic hypoaldosteronism），且伴隨高血鉀（hyperkalemia）症候群。在高鉀離子飲食攝入的壓力下，Rrbp1基因剔除小鼠表現出嚴重的高血鉀誘發心律不整（arrhythmia），並顯著增加死亡率。然而，透過氟氫可體松（Fludrocortisone）的治療，可以有效降低Rrbp1基因剔除小鼠在高鉀離子飲食攝入後的血鉀濃度以及死亡率。 此外，利用免疫組織化學染色法標定腎臟切片中腎素發現在Rrbp1基因剔除小鼠之腎臟組織切片的腎素含量明顯高於野生型小鼠。相似的是，我們利用免疫金染色標定RRBP1基因敲弱（RRBP1-kcockdown）的人類腎素生產細胞株（Calu-6）之腎素發現RRBP1基因敲弱後，腎素大量累積在細胞內。同時，免疫螢光染色發現RRBP1基因敲弱後，影響了腎素從內質網運輸到高基氏體的效率。本研究發現RRBP1藉由影響腎素在細胞內的運輸調控生理血壓以及血鉀扮演重要的角色。 | zh_TW |
| dc.description.abstract | RRBP1, also known as ER ribosomal-binding protein 1 or p180, has been implicated in various cardiovascular diseases through genetic variants identified in numerous genome-wide association studies. However, the precise role of RRBP1 in the regulation of blood pressure remains undefined. In this study, we aimed to elucidate the impact of RRBP1 on blood pressure regulation and its role in cardiovascular physiology.
In the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort, our research team conducted a genome-wide linkage analysis followed by regional fine mapping. This comprehensive approach enabled us to identify noteworthy genetic variants within the RRBP1 gene, demonstrating a significant association with blood pressure. To investigate the functional implications of RRBP1, we generated a transgenic mouse model. Rrbp1-knockout mice exhibited lower blood pressure and increased susceptibility to sudden cardiac death, which was attributed to hyporeninemic hypoaldosteronism-induced hyperkalemia. Significantly, when subjected to high potassium intake, Rrbp1-knockout mice exhibited a noteworthy decrease in survival rate compared to their wild-type counterparts. Remarkably, these Rrbp1-knockout mice displayed severe lethal arrhythmia induced by hyperkalemia and persistent hypoaldosteronism, particularly under conditions of elevated potassium intake. However, treatment with fludrocortisone effectively rescued these phenotypes. Immunohistochemistry analysis revealed the accumulation of renin within the kidneys of Rrbp1-knockout mice, indicating impaired renin-angiotensin-aldosterone system (RAAS) function. Furthermore, our investigations confirmed that renin predominantly accumulated within the endoplasmic reticulum (ER) and exhibited compromised transport to the Golgi apparatus in RRBP1-knockdown (-KD) Calu-6 cells. This impaired secretion of renin was substantiated through detailed examinations using transmission electron and confocal microscopy. In parallel, our human genetic studies revealed a significant association between RRBP1 genetic variants and blood pressure. Notably, consistent with the findings in our mouse model, mice lacking RRBP1 exhibited lower levels of plasma renin and aldosterone, resulting in reduced blood pressure, severe hyperkalemia, and cardiac sudden death. Collectively, our study provides novel insights into the role of RRBP1 as a modulator of the renin-angiotensin-aldosterone system (RAAS), affecting blood pressure regulation and potassium homeostasis. | en |
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| dc.description.tableofcontents | Table of contents
口試委員會審定書 ii 誌謝 iii 摘要 iv Abstract-vi Table of contents viii List of figures xii List of tables xiv Chapter 1: Introduction 1 1-1 Cardiovascular diseases 1 1-2 Hypertension 1 1-3 Renin-angiotensin-aldosterone system 2 1-4 Renin 3 1-5 RRBP1 5 1-6 Genetic variants of RRBP1 in CVDs 6 Chapter 2: Results and Figure legends 8 2-1 RRBP1 genetic variants are associated with blood pressure in various studies 8 2-2 Creation of Rrbp1-knockout mice 11 2-3 The basal phenotypes of Rrbp1-knockout mice 14 2-4 The deficiency of RRBP1 result in lower blood pressure and an increased rate of sudden death 16 2-5 The heart function and structure of Rrbp1-knockout mice display no significant difference compared with those of Rrbp1-WT mice 19 2-6 The basal plasma potassium level of Rrbp1-knockout mice is higher than that of control mice 21 2-7 The sudden death of Rrbp1-knockout mice increases dramatically under high K+ intake within 30 days 23 2-8 The ECG waveform of Rrbp1-knockout mice is disturbed under high K+ intake for 2 days 26 2-9 Rrbp1-knockout mice display hyporeninemic hypoaldosteronism 29 2-10 The adrenal gland function of Rrbp1-knockout mice has no significant difference with that of Rrbp1-WT mice 32 2-11 The plasma renin, angiotensin-II, and aldosterone are still lower in Rrbp1-knockout mice under high K+ intake for 2 days 34 2-12 High K+ load-induced hyperkalemia and sudden death in Rrbp1-knockout mice can be rescued by fludrocortisone treatment 36 2-13 The expression of renin is higher within the kidney section of Rrbp1-knockout mice 39 2-14 The higher expression of intracellular renin and lower of secreted renin of RRBP1-KD cells 41 2-15 There were less renin particles near plasma membrane of RRBP1-KD cells 43 2-16 RRBP1 regulated renin secretion is in a cAMP-independent pathway 46 2-17 Deficiency of RRBP1 results in accumulation of renin in endoplasmic reticulum 49 2-18 Deficiency of RRBP1 lead to hyporeninemic hypoaldosteronism, hypotension, and hyperkalemia 57 Chapter 3: Discussion 59 Chapter 4: Material and methods 65 4-1 The Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort 65 4-2 Genome-wide linkage and Family-based association analyses for identification of blood pressure regulation gene 65 4-3 Generation of Rrbp1-knockout mice 66 4-4 Western blot analysis 67 4-5 Body composition analysis 68 4-6 Intracranial vessel scanning by magnetic resonance angiograph 68 4-7 Telemetry ECG and blood pressure measurement 69 4-8 Blood and urine analysis 69 4-9 ACTH stimulation test 70 4-10 Real-time quantitative PCR (RT-qPCR) 70 4-11 Renal Immunohistochemistry 72 4-12 Calu-6 cell culture 73 4-13 Lentiviral transfection 73 4-14 Immuno-electron microscopy 73 4-15 Immunofluorescence stain 74 4-16 Statistics 75 Chapter 5: References 77 List of figures 1. Figure 1. Creation of Rrbp1-knockout mice 12 2. Figure 2. The basal phenotypes of Rrbp1-knockout mice 15 3. Figure 3. The blood pressure and survival rate of Rrbp1-knockout mice 17 4. Figure 4. The echocardiogram analysis of mice 20 5. Figure 5. The survival rate of Rrbp1-WT and Rrbp1-knockout mice under high K+ intake 24 6. Figure 6. The telemetry ECG of Rrbp1-WT and Rrbp1-knockout mice before and after high K+ intake 27 7. Figure 7. Hyporeninemic hypoaldosteronism of Rrbp1-knockout mice 30 8. Figure 8. The adrenal function of Rrbp1-knockout mice 33 9. Figure 9. The RAAS level of Rrbp1-knockout mice under high K+ intake for 2 days 35 10. Figure 10. The survival rate of Rrbp1-knockout mice under high K+ intake with Fludrocortisone treatment 37 11. Figure 11. The renin intensity in the kidney sections of Rrbp1-WT and Rrbp1-knockout mice 40 12. Figure 12. Renin distribution of RRBP1-KD cells 42 13. Figure 13. The immunogold-labeled renin staining by transmission electron microscopy 44 14. Figure 14. Forskolin treatment on control and RRBP1-KD Calu-6 cells 47 15. Figure 15. Intracellular renin trafficking in RRBP1-KD cells 50 16. Figure 16. Schematic diagram of the mechanism by which RRBP1 affects renin trafficking and secretion 58 List of tables 1. Table 1. The relationship between blood pressure and a 7-SNP haplotype (re7272683, rs2236255, rs6034875, rs6080761, rs6080765, rs812079, rs3790308) within the RRBP1 gene by FBAT analysis 10 2. Table 2. Plasma and urine electrolyte levels for Rrbp1-WT and Rrbp1-knockout mice 22 3. Table 3. Plasma and urine electrolyte levels for Rrbp1-WT and Rrbp1-knockout mice under high K+ intake 25 4. Table 4. Plasma and urine electrolyte levels for Rrbp1-WT and Rrbp1-knockout mice under high K+ intake for 48 hours with and without fludrocortisone treatment 38 | - |
| dc.language.iso | en | - |
| dc.title | RRBP1透過調控腎素之胞內運輸調節血壓及鉀離子恆定 | zh_TW |
| dc.title | RRBP1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 莊立民;林石化;吳允升;潘思樺 | zh_TW |
| dc.contributor.oralexamcommittee | Lee-Ming Chuang;Shih-Hua Lin;Vincent Wu;Szu-Hua Pan | en |
| dc.subject.keyword | RRBP1,血壓,腎素,高血鉀,心律不整,猝死, | zh_TW |
| dc.subject.keyword | Arrhythmia,blood pressure,hyperkalemia,renin,RRBP1,sudden death, | en |
| dc.relation.page | 90 | - |
| dc.identifier.doi | 10.6342/NTU202301026 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2023-06-17 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 基因體暨蛋白體醫學研究所 | - |
| 顯示於系所單位： | 基因體暨蛋白體醫學研究所 | |
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