Dokument: Auswirkung kardiovaskulärer Risikofaktoren auf die erythrokrine Funktion im Ischämie-/ Reperfusionsschaden am Langendorff-Transfermodell
| Titel: | Auswirkung kardiovaskulärer Risikofaktoren auf die erythrokrine Funktion im Ischämie-/ Reperfusionsschaden am Langendorff-Transfermodell | |||||||
| Weiterer Titel: | Impact of cardiovascular risk factors on erythrocrine function in the setting of ischemia/ reperfusion-injury in a Langendorff heart model | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=57897 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20211116-110815-7 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Möllhoff, Luise [Autor] | |||||||
| Dateien: |
| |||||||
| Beitragende: | Prof. Dr. Jung, Christian [Gutachter] Prof. Dr. med. Akhyari, Payam [Gutachter] | |||||||
| Stichwörter: | erythrokrine Funktion, Arginase, eNOS, L-NAME, norNOHA, red blood cells, Erythrozyten, Myokardinfarkt | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Der ischämische Myokardinfarkt, verursacht durch den Verschluss eines koronaren Gefäßes, ist weltweit eine der führenden Todesursachen. Doch auch die Reperfusion nach interventioneller Revaskularisierung verursacht Schäden am Myokard. Im Zusammenhang mit diesen sogenannten Ischämie-/ Reperfusionsschäden (I/R-Schäden) kann Stickstoff-monoxid (NO) kardioprotektiv wirken. Eine endogene Hauptquelle des NO ist die endotheliale NO-Synthase (eNOS), die zur NO-Produktion ebenso wie die Arginase das Substrat L-Arginin verwendet. Im Rahmen einer endothelialen Dysfunktion ist die Arginase-Aktivität gesteigert, wodurch der eNOS weniger Substrat für die NO-Produktion zur Verfügung steht. Neben den Endothelzellen werden beide Enzyme auch in Erythrozyten (RBCs) exprimiert.
In dieser Arbeit sollte die Wirkung humaner RBCs auf murine Herzen in einem ex vivo Langendorff-Transfermodell untersucht und die Interaktion der eNOS und Arginase in RBCs genauer charakterisiert werden. Zudem sollte der Einfluss kardiovaskulärer Risikofaktoren auf dieses Zusammenspiel untersucht werden. Dafür wurden RBCs junger Probanden sowie älterer, kardiologisch behandelter Patienten mit einem Diabetes Mellitus Typ 2 vor und nach Behandlung mit den Enzyminhibitoren norNOHA und/ oder L-NAME in die Koronarien muriner Herzen geladen. Die Herzen wurden einer 40-minütigen Ischämie unterzogen, der eine 120-minütige Reperfusionsphase folgte. Untersucht wurden die funktionellen und strukturellen Veränderungen der Herzen. Humane RBCs konnten im Vergleich zu Puffer-perfundierten Kontrollen die myokardiale Funktionserhaltung der murinen Herzen nach 60-minütiger Reperfusion verbessern sowie die Infarktgröße nach 120 Minuten Reperfusion verringern. Unter Perfusion mit RBCs diabetischer Patienten war die myokardiale Druckentwicklung nach I/R eingeschränkt verglichen mit der der mit RBCs junger Probanden perfundierten Herzen. Eine Arginase-Inhibition in RBCs diabetischer Probanden mittels norNOHA führte zu einer Verringerung der Infarktgröße und Verbesserung der myokardialen Funktion. Eine zusätzliche Hemmung der eNOS mittels L-NAME hob diesen Effekt wieder auf. Die Hemmung der Enzyme in RBCs junger Probanden verschlechterte das Outcome nach I/R. Die Ergebnisse dieser Arbeit zeigen, dass die Arginase-Aktivität bei Vorliegen kardiovaskulärer Risikofaktoren auch in RBCs zu einer Einschränkung der eNOS-Aktivität, einer erythrozytären Dysfunktion, führt. Durch Inhibition der Arginase lässt sich die eNOS-Funktion wieder verbessern. Die Arginase-Inhibition stellt somit ein potentielles pharmakologisches Target für die Therapie des Myokardinfarkts dar.Myocardial infarction (MI) is one of the leading causes of deaths worldwide. During MI, the ischemia and the reperfusion after intervention both cause myocardial damages called ischemia/ reperfusion-injury (I/R-injury). Nitric oxide (NO) can protect the myocardium from I/R-injury. An important source of NO is the endothelial NO-synthase (eNOS), which can be inhibited indirectly by the enzyme arginase as both compete for their common substrate l-arginine. In endothelial dysfunction the activity of arginase is increased. An inhibition of arginase leads to an increase in NO availability and thereby to smaller I/R-injuries. It was shown that not only endothelial cells but also red blood cells (RBCs) express both enzymes. Using an ex vivo Langendorff system, this study examines the impact of human RBCs on murine hearts and characterizes the interaction of RBC eNOS and arginase. It further focuses on the impact of cardiovascular risk factors within this interaction. RBCs were obtained from healthy young volunteers and elderly patients with cardiovascular disease or peripheral artery disease and diabetes mellitus type 2. The RBCs were treated with vehicle or the enzyme inhibitors norNOHA and/ or L-NAME and loaded into the coronary system of the murine hearts, where 40 minutes of global ischemia were followed by 120 minutes of reperfusion. During the experiment, functional and structural changes were analyzed. Compared to vehicle-perfused controls, human RBCs of young volunteers improved myocardial function after 60 minutes of reperfusion and reduced infarct size after 120 minutes of reperfusion. Perfusion with RBCs of diabetic patients impaired myocardial function after I/R compared to perfusion with RBCs of young volunteers. An arginase-inhibition in diabetic RBCs due to norNOHA reduced infarct size and improved myocardial function. An additional inhibition of eNOS using L-NAME abolished this effect. In contrast, enzyme-inhibition in young RBCs showed a poor outcome after I/R. The results of this study show that arginase-activity impairs eNOS function also in RBCs of elderly diabetic patients, indicating an erythrocrine dysfunction. Arginase-inhibition in RBCs restores eNOS function representing a potential pharmacological target in the treatment of MI. | |||||||
| Quelle: | ANDREADOU, I., ILIODROMITIS, E. K., RASSAF, T., SCHULZ, R., PAPAPETROPOULOS, A. & FERDINANDY, P. 2015. The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning. British Journal of Pharmacology, 172, 1587-1606.
BASALAY, M., BARSUKEVICH, V., MASTITSKAYA, S., MROCHEK, A., PERNOW, J., SJOQUIST, P. O., ACKLAND, G. L., GOURINE, A. V. & GOURINE, A. 2012. Remote ischaemic pre- and delayed postconditioning - similar degree of cardioprotection but distinct mechanisms. Experimental Physiology, 97, 908-917. BELL, R. M., MOCANU, M. M. & YELLON, D. M. 2011. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol, 50, 940-50. BOATENG, S. & SANBORN, T. 2013. Acute myocardial infarction. Dis Mon, 59, 83-96. BONNER, G. 1997. The role of kinins in the antihypertensive and cardioprotective effects of ACE inhibitors. Drugs, 54, 23-30. BRAUNWALD, E. & KLONER, R. A. 1985. Myocardial Reperfusion - a Double-Edged Sword. Journal of Clinical Investigation, 76, 1713-1719. BRYAN, N. S. & GRISHAM, M. B. 2007. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med, 43, 645-57. CHEN, L. Y. & MEHTA, J. L. 1998. Evidence for the presence of L-arginine-nitric oxide pathway in human red blood cells: relevance in the effects of red blood cells on platelet function. J Cardiovasc Pharmacol, 32, 57-61. CORTESE-KROTT, M. M. & KELM, M. 2014. Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function? Redox Biol, 2, 251-8. CORTESE-KROTT, M. M., MERGIA, E., KRAMER, C. M., LUCKSTADT, W., YANG, J., WOLFF, G., PANKNIN, C., BRACHT, T., SITEK, B., PERNOW, J., STASCH, J. P., FEELISCH, M., KOESLING, D. & KELM, M. 2018. Identification of a soluble guanylate cyclase in RBCs: preserved activity in patients with coronary artery disease. Redox Biol, 14, 328-337. CORTESE-KROTT, M. M., RODRIGUEZ-MATEOS, A., SANSONE, R., KUHNLE, G. G. C., THASIAN-SIVARAJAH, S., KRENZ, T., HORN, P., KRISP, C., WOLTERS, D., HEISS, C., KRONCKE, K. D., HOGG, N., FEELISCH, M. & KELM, M. 2012. Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease. Blood, 120, 4229-4237. DEWOOD, M. A., SPORES, J., NOTSKE, R., MOUSER, L. T., BURROUGHS, R., GOLDEN, M. S. & LANG, H. T. 1980. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med, 303, 897-902. DURANTE, W., JOHNSON, F. K. & JOHNSON, R. A. 2007. Arginase: a critical regulator of nitric oxide synthesis and vascular function. Clin Exp Pharmacol Physiol, 34, 906-11. ELIGINI, S., PORRO, B., LUALDI, A., SQUELLERIO, I., VEGLIA, F., CHIORINO, E., CRISCI, M., GARLASCHE, A., GIOVANNARDI, M., WERBA, J. P., TREMOLI, E. & CAVALCA, V. 2013. Nitric Oxide Synthetic Pathway in Red Blood Cells Is Impaired in Coronary Artery Disease. Plos One, 8. ESPER, R. J., VILARINO, J. O., MACHADO, R. A. & PARAGANO, A. 2008. Endothelial dysfunction in normal and abnormal glucose metabolism. Adv Cardiol, 45, 17-43. FORSTERMANN, U. & SESSA, W. C. 2012. Nitric oxide synthases: regulation and function. Eur Heart J, 33, 829-37, 837a-837d. FRANK, A., BONNEY, M., BONNEY, S., WEITZEL, L., KOEPPEN, M. & ECKLE, T. 2012. Myocardial ischemia reperfusion injury: from basic science to clinical bedside. Semin Cardiothorac Vasc Anesth, 16, 123-32. FURCHGOTT, R. F. & VANHOUTTE, P. M. 1989. Endothelium-Derived Relaxing and Contracting Factors. Faseb Journal, 3, 2007-2018. GONON, A. T., JUNG, C., KATZ, A., WESTERBLAD, H., SHEMYAKIN, A., SJOQUIST, P. O., LUNDBERG, J. O. & PERNOW, J. 2012. Local arginase inhibition during early reperfusion mediates cardioprotection via increased nitric oxide production. PLoS One, 7, e42038. GONZALES, T. K., YONKER, J. A., CHANG, V., ROAN, C. L., HERD, P. & ATWOOD, C. S. 2017. Myocardial infarction in the Wisconsin Longitudinal Study: the interaction among environmental, health, social, behavioural and genetic factors. Bmj Open, 7. GRONROS, J., KISS, A., PALMER, M., JUNG, C., BERKOWITZ, D. & PERNOW, J. 2013. Arginase inhibition improves coronary microvascular function and reduces infarct size following ischaemia-reperfusion in a rat model. Acta Physiol (Oxf), 208, 172-9. HAMMOND, J. & BALLIGAND, J. L. 2012. Nitric oxide synthase and cyclic GMP signaling in cardiac myocytes: from contractility to remodeling. J Mol Cell Cardiol, 52, 330-40. HAUSENLOY, D. J. & YELLON, D. M. 2013. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. Journal of Clinical Investigation, 123, 92-100. HERNANDEZ-PERERA, O., PEREZ-SALA, D., NAVARRO-ANTOLIN, J., SANCHEZ-PASCUALA, R., HERNANDEZ, G., DIAZ, C. & LAMAS, S. 1998. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. Journal of Clinical Investigation, 101, 2711-2719. HERR, D. J., AUNE, S. E. & MENICK, D. R. 2015. Induction and Assessment of Ischemia-reperfusion Injury in Langendorff-perfused Rat Hearts. J Vis Exp, e52908. HERRICK, J. B. 1983. Landmark article (JAMA 1912). Clinical features of sudden obstruction of the coronary arteries. By James B. Herrick. JAMA, 250, 1757-65. HIMENO, M., ISHIBASHI, T., NAKANO, S., FURUYA, K., YOSHIDA, J., KIGOSHI, T., UCHIDA, K. & NISHIO, M. 2004. Implication of steady state concentrations of nitrite and nitrate metabolites of nitric oxide in plasma and whole blood in healthy human subjects. Clin Exp Pharmacol Physiol, 31, 591-6. IBANEZ, B., JAMES, S., AGEWALL, S., ANTUNES, M. J., BUCCIARELLI-DUCCI, C., BUENO, H., CAFORIO, A. L. P., CREA, F., GOUDEVENOS, J. A., HALVORSEN, S., HINDRICKS, G., KASTRATI, A., LENZEN, M. J., PRESCOTT, E., ROFFI, M., VALGIMIGLI, M., VARENHORST, C., VRANCKX, P., WIDIMSKY, P., COLLET, J. P., KRISTENSEN, S. D., ABOYANS, V., BAUMBACH, A., BUGIARDINI, R., COMAN, I. M., DELGADO, V., FITZSIMONS, D., GAEMPERLI, O., GERSHLICK, A. H., GIELEN, S., HARJOLA, V. P., KATUS, H. A., KNUUTI, J., KOLH, P., LECLERCQ, C., LIP, G. Y. H., MORAIS, J., NESKOVIC, A. N., NEUMANN, F. J., NIESSNER, A., PIEPOLI, M. F., RICHTER, D. J., SHLYAKHTO, E., SIMPSON, I. A., STEG, P. G., TERKELSEN, C. J., THYGESEN, K., WINDECKER, S., ZAMORANO, J. L., ZEYMER, U. & CARDIOLOGY, E. S. 2018. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal, 39, 119-+. IGNARRO, L. J., BUGA, G. M., WOOD, K. S., BYRNS, R. E. & CHAUDHURI, G. 1987. Endothelium-Derived Relaxing Factor Produced and Released from Artery and Vein Is Nitric-Oxide. Proceedings of the National Academy of Sciences of the United States of America, 84, 9265-9269. ISHIBASHI, T., KUBOTA, K., HIMENO, M., MATSUBARA, T., HORI, T., OZAKI, K., YAMOZOE, M., AIZAWA, Y., YOSHIDA, J. & NISHIO, M. 2001. Respiratory alkalosis does not alter NOx concentrations in human plasma and erythrocytes. Am J Physiol Heart Circ Physiol, 281, H2757-61. JENNINGS, R. B., SOMMERS, H. M., SMYTH, G. A., FLACK, H. A. & LINN, H. 1960. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol, 70, 68-78. JONES, S. P. & BOLLI, R. 2006. The ubiquitous role of nitric oxide in cardioprotection. J Mol Cell Cardiol, 40, 16-23. JUNG, C., GONON, A. T., SJOQUIST, P. O., LUNDBERG, J. O. & PERNOW, J. 2010. Arginase inhibition mediates cardioprotection during ischaemia-reperfusion. Cardiovasc Res, 85, 147-54. KEMP, C. D. & CONTE, J. V. 2012. The pathophysiology of heart failure. Cardiovascular Pathology, 21, 365-371. KIM, J. H., BUGAJ, L. J., OH, Y. J., BIVALACQUA, T. J., RYOO, S., SOUCY, K. G., SANTHANAM, L., WEBB, A., CAMARA, A., SIKKA, G., NYHAN, D., SHOUKAS, A. A., ILIES, M., CHRISTIANSON, D. W., CHAMPION, H. C. & BERKOWITZ, D. E. 2009. Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats. J Appl Physiol (1985), 107, 1249-57. KLEINBONGARD, P., DEJAM, A., LAUER, T., RASSAF, T., SCHINDLER, A., PICKER, O., SCHEEREN, T., GODECKE, A., SCHRADER, J., SCHULZ, R., HEUSCH, G., SCHAUB, G. A., BRYAN, N. S., FEELISCH, M. & KELM, M. 2003. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radical Biology and Medicine, 35, 790-796. KLEINBONGARD, P., SCHULZ, R., MUENCH, M., RASSAF, T., LAUER, T., GOEDECKE, A. & KELM, M. 2006. Red blood cells express a functional endothelial nitric oxide synthase. European Heart Journal, 27, 127-127. KNOWLES, R. G. & MONCADA, S. 1992. Nitric-Oxide as a Signal in Blood-Vessels. Trends in Biochemical Sciences, 17, 399-402. KOVAMEES, O., SHEMYAKIN, A., CHECA, A., WHEELOCK, C. E., LUNDBERG, J. O., OSTENSON, C. G. & PERNOW, J. 2016. Arginase Inhibition Improves Microvascular Endothelial Function in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab, 101, 3952-3958. KOVAMEES, O., SHEMYAKIN, A. & PERNOW, J. 2014. Effect of Arginase Inhibition on Ischemia-Reperfusion Injury in Patients with Coronary Artery Disease with and without Diabetes Mellitus. Plos One, 9. LANGENDORFF, O. 1895. Untersuchungen am überlebenden Säugethierherzen. Pflügers Arch., 61, 291 doi:10.1007/BF01812150. LAUER, T., PREIK, M., RASSAF, T., STRAUER, B. E., DEUSSEN, A., FEELISCH, M. & KELM, M. 2001. Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proceedings of the National Academy of Sciences of the United States of America, 98, 12814-12819. MAHDI, A., JIAO, T., YANG, J. N., KOVAMEES, O., ALVARSSON, M., VON HEIJNE, M., ZHOU, Z. C. & PERNOW, J. 2019a. The Effect of Glycemic Control on Endothelial and Cardiac Dysfunction Induced by Red Blood Cells in Type 2 Diabetes. Frontiers in Pharmacology, 10. MAHDI, A., KOVAMEES, O., CHECA, A., WHEELOCK, C. E., VON HEIJNE, M., ALVARSSON, M. & PERNOW, J. 2018. Arginase inhibition improves endothelial function in patients with type 2 diabetes mellitus despite intensive glucose-lowering therapy. Journal of Internal Medicine, 284, 388-398. MAHDI, A., PERNOW, J. & K?VAMEES, O. 2019b. Arginase Inhibition Improves Endothelial Function in an Age-Dependent Manner in Healthy Elderly Humans. Rejuvenation Research, 22, 385-389. MAHMOOD, S. S., LEVY, D., VASAN, R. S. & WANG, T. J. 2014. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet, 383, 999-1008. MERX, M. W., GORRESSEN, S., VAN DE SANDT, A. M., CORTESE-KROTT, M. M., OHLIG, J., STERN, M., RASSAF, T., GODECKE, A., GLADWIN, M. T. & KELM, M. 2014. Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction. Basic Res Cardiol, 109, 398. MOENS, A. L., CLAEYS, M. J., TIMMERMANS, J. P. & VRINTS, C. J. 2005. Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. Int J Cardiol, 100, 179-90. MONCADA, S. & HIGGS, A. 1993. The L-arginine-nitric oxide pathway. N Engl J Med, 329, 2002-12. MONCADA, S., PALMER, R. M. & HIGGS, E. A. 1991. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev, 43, 109-42. MUESSIG, J. M., KAYA, S., MOELLHOFF, L., NOELLE, J., HIDALGO PAREJA, L., MASYUK, M., GERDES, N., PERNOW, J., KELM, M. & JUNG, C. 2020a. A Model of Blood Component-Heart Interaction in Cardiac Ischemia-Reperfusion Injury using a Langendorff-Based Ex Vivo Assay. J Cardiovasc Pharmacol Ther, 25, 164-173. MUESSIG, J. M., MOELLHOFF, L., NOELLE, J., KAYA, S., HIDALGO PAREJA, L., MASYUK, M., RODEN, M., KELM, M. & JUNG, C. 2020b. Poor glycemic control impairs the cardioprotective effects of red blood cells on myocardial ischemia/reperfusion injury. Nitric Oxide, 97, 1-10. OPIE, L. H. 1989. Reperfusion injury and its pharmacologic modification. Circulation, 80, 1049-62. PERNOW, J. & JUNG, C. 2013. Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal? Cardiovasc Res, 98, 334-43. PORRO, B., ELIGINI, S., SQUELLERIO, I., TREMOLI, E. & CAVALCA, V. 2014. The red blood cell: a new key player in cardiovascular homoeostasis? Focus on the nitric oxide pathway. Biochem Soc Trans, 42, 996-1000. RASSAF, T., POLL, L. W., BROUZOS, P., LAUER, T., TOTZECK, M., KLEINBONGARD, P., GHARINI, P., ANDERSEN, K., SCHULZ, R., HEUSCH, G., MODDER, U. & KELM, M. 2006. Positive effects of nitric oxide on left ventricular function in humans. Eur Heart J, 27, 1699-705. REED, G. W., ROSSI, J. E. & CANNON, C. P. 2017. Acute myocardial infarction. Lancet, 389, 197-210. SANADA, S., KOMURO, I. & KITAKAZE, M. 2011. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. American Journal of Physiology-Heart and Circulatory Physiology, 301, H1723-H1741. SCHULZ, R., KELM, M. & HEUSCH, G. 2004. Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc Res, 61, 402-13. SKRZYPIEC-SPRING, M., GROTTHUS, B., SZELAG, A. & SCHULZ, R. 2007. Isolated heart perfusion according to Langendorff---still viable in the new millennium. J Pharmacol Toxicol Methods, 55, 113-26. SPECTOR, E. B., RICE, S. C., KERN, R. M., HENDRICKSON, R. & CEDERBAUM, S. D. 1985. Comparison of arginase activity in red blood cells of lower mammals, primates, and man: evolution to high activity in primates. Am J Hum Genet, 37, 1138-45. STATISTISCHES BUNDESAMT DESTATIS 2017. Gesundheit Todesursachen in Deutschland. DESTATIS wissen. nutzen. STRIJDOM, H., CHAMANE, N. & LOCHNER, A. 2009. Nitric oxide in the cardiovascular system: a simple molecule with complex actions. Cardiovasc J Afr, 20, 303-10. STUEHR, D. J. 2004. Enzymes of the L-arginine to nitric oxide pathway. J Nutr, 134, 2748S-2751S; discussion 2765S-2767S. SUTHERLAND, F. J. & HEARSE, D. J. 2000. The isolated blood and perfusion fluid perfused heart. Pharmacol Res, 41, 613-27. SUTHERLAND, F. J., SHATTOCK, M. J., BAKER, K. E. & HEARSE, D. J. 2003. Mouse isolated perfused heart: characteristics and cautions. Clin Exp Pharmacol Physiol, 30, 867-78. THYGESEN, K., ALPERT, J. S., JAFFE, A. S., CHAITMAN, B. R., BAX, J. J., MORROW, D. A., WHITE, H. D. & GROUP, E. S. C. S. D. 2018. Fourth universal definition of myocardial infarction (2018). Eur Heart J. TOTZECK, M., HENDGEN-COTTA, U. B., FRENCH, B. A. & RASSAF, T. 2016. A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury. J Biol Methods, 3. TSIKAS, D. 2007. Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J Chromatogr B Analyt Technol Biomed Life Sci, 851, 51-70. TSUTSUI, M., SHIMOKAWA, H., OTSUJI, Y. & YANAGIHARA, N. 2010. Pathophysiological relevance of NO signaling in the cardiovascular system: Novel insight from mice lacking all NO synthases. Pharmacology & Therapeutics, 128, 499-508. ULKER, P., GUNDUZ, F., MEISELMAN, H. J. & BASKURT, O. K. 2013. Nitric oxide generated by red blood cells following exposure to shear stress dilates isolated small mesenteric arteries under hypoxic conditions. Clin Hemorheol Microcirc, 54, 357-69. WEBB, A. J., MILSOM, A. B., RATHOD, K. S., CHU, W. L., QURESHI, S., LOVELL, M. J., LECOMTE, F. M. J., PERRETT, D., RAIMONDO, C., KHOSHBIN, E., AHMED, Z., UPPAL, R., BENJAMIN, N., HOBBS, A. J. & AHLUWALIA, A. 2008. Mechanisms Underlying Erythrocyte and Endothelial Nitrite Reduction to Nitric Oxide in Hypoxia Role for Xanthine Oxidoreductase and Endothelial Nitric Oxide Synthase. Circulation Research, 103, 957-U114. WHO. 2020. Leading causes of death and disability/ A visual summary of global and regional trends 2000-2019 [Online]. Available: https://www.who.int/data/stories/leading-causes-of-death-and-disability-2000-2019-a-visual-summary [Accessed 2021/01/26]. WILANSKY, S., MORENO, C. A. & LESTER, S. J. 2007. Complications of myocardial infarction. Crit Care Med, 35, S348-54. WOOD, K. C., CORTESE-KROTT, M. M., KOVACIC, J. C., NOGUCHI, A., LIU, V. B., WANG, X., RAGHAVACHARI, N., BOEHM, M., KATO, G. J., KELM, M. & GLADWIN, M. T. 2013. Circulating blood endothelial nitric oxide synthase contributes to the regulation of systemic blood pressure and nitrite homeostasis. Arterioscler Thromb Vasc Biol, 33, 1861-71. YANG, B. C., NICHOLS, W. W. & MEHTA, J. L. 1996. Cardioprotective Effects of Red Blood Cells on Ischemia and Reperfusion Injury in Isolated Rat Heart: Release of Nitric Oxide as a Potential Mechanism. J Cardiovasc Pharmacol Ther, 1, 297-306. YANG, J., GONON, A. T., SJOQUIST, P. O., LUNDBERG, J. O. & PERNOW, J. 2013. Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity. Proc Natl Acad Sci U S A, 110, 15049-54. YANG, J., ZHENG, X., MAHDI, A., ZHOU, Z., TRATSIAKOVICH, Y., JIAO, T., KISS, A., KOVAMEES, O., ALVARSSON, M., CATRINA, S. B., LUNDBERG, J. O., BRISMAR, K. & PERNOW, J. 2018. Red Blood Cells in Type 2 Diabetes Impair Cardiac Post-Ischemic Recovery Through an Arginase-Dependent Modulation of Nitric Oxide Synthase and Reactive Oxygen Species. JACC Basic Transl Sci, 3, 450-463. YUSUF, S., HAWKEN, S. & OUNPUU, S. 2004. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study (vol 364, pg 937m 2004). Lancet, 364, 2020-2020. ZHOU, Z. C., MAHDI, A., TRATSIAKOVICH, Y., ZAHORAN, S., KOVAMEES, O., NORDIN, F., GONZALEZ, A. E. U., ALVARSSON, M., OSTENSON, C. G., ANDERSSON, D. C., HEDIN, U., HERMESZ, E., LUNDBERG, J. O., YANG, J. N. & PERNOW, J. 2018. Erythrocytes From Patients With Type 2 Diabetes Induce Endothelial Dysfunction Via Arginase I. Journal of the American College of Cardiology, 72, 769-780. ZIOLO, M. T., KOHR, M. J. & WANG, H. 2008. Nitric oxide signaling and the regulation of myocardial function. J Mol Cell Cardiol, 45, 625-32. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Bezug: | 2021 | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 16.11.2021 | |||||||
| Dateien geändert am: | 16.11.2021 | |||||||
| Promotionsantrag am: | 03.03.2021 | |||||||
| Datum der Promotion: | 07.10.2021 |
