Dokument: αIIbβ3-abhängige Plättchenadhäsion an mutierten und Wildtyp-von Willebrand-Faktor bei unterschiedlichen Scherraten
| Titel: | αIIbβ3-abhängige Plättchenadhäsion an mutierten und Wildtyp-von Willebrand-Faktor bei unterschiedlichen Scherraten | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=62447 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20230424-092053-1 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Bleyer, Vivian [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Schelzig, Hubert [Gutachter] Prof. Dr. med. Hohlfeld, Thomas [Gutachter] | |||||||
| Stichwörter: | HPA-1-Polymorphimus F/Y2561-vWF-Polymorphimus | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Im Kontext der in westlichen Ländern sehr häufigen Koronaren Herzkrankheit (KHK) kann die Entstehung von arteriellen Thrombosen ein zentrales Merkmal der Pathogenese dieser Erkrankung sein.
In dieser Arbeit sollten die Auswirkungen zweier spezieller Polymorphismen auf die Hämostase untersucht werden, die den von-Willebrand-Faktor und das Thrombozyten-Integrin αIIbβ3 betreffen, wobei das besondere Augenmerk auf den Phenylalanin/Tyrosin-Polymorphismus (F2561-/ Y2561-Variante) des von-Willebrand-Faktors gelegt wurde. Mittels lasermikroskopischer Beobachtung von fluoreszierenden Thrombozyten konnten Qualität und Quantität der Thrombozytenadhäsion auf unterschiedlichen von-Willebrand-Faktor-Präparaten beurteilt werden. Dass die dokumentierte Thrombozytenadhäsion zweifelsfrei durch die Interaktion des von-Willebrand-Faktors mit dem Integrin αIIbβ3 bedingt war, wurde im Vorfeld mit Antikörper-Experimenten belegt. In Versuchen mit Probandenblut des Merkmals HPA-1a1a für das Integrins αIIbβ3 stellte sich heraus, dass auf immobilisiertem F2561-vWF (Wildtyp) eine höhere Adhäsion zu registrieren war, als auf der Y2561-Variante dieses Gerinnungsfaktors. Dieses Resultat kann die ursprüngliche These, dass für den von Hellermann et al. [9] wahrgenommenen Zusammenhang zwischen dem vermehrten Auftreten eines Myokardinfarktes bei unter 55-jährigen Frauen und dem Vorliegen der Y2561-Variante des von-Willebrand-Faktors bei diesen Patientinnen ein erhöhtes Risiko arterieller Thrombosen ursächlich war, nicht unterstützen. Weiterhin ließen die Versuchsergebnisse die Vermutung aufkommen, dass unter einer höheren Scherrate von 1000 s-1, wie sie beispielsweise in Koronararterien auftritt, eine Thrombozytenadhäsion auf mutiertem von-Willebrand-Faktor geringer war. Die Untersuchung des Einflusses ansteigender Scherraten zeigte für die F2561-Variante des von-Willebrand-Faktors im Gegensatz zu der Y2561-vWF-Variante ein etwa gleichbleibendes Maß an Thrombozytenadhäsion, somit unterstreicht dieser Versuchsausgang seine erhaltene physiologische Funktion der Blutungsstillung.In the western world, Coronary Artery Disease (CAD, or Coronary Heart Disease, CHD) is a common illness. Arterial embolism can occur as a central aspect in its pathogenesis. This dissertation was designed to explore the impact of two specific polymorphisms in haemostaseologic function, concerning von Willebrand Factor and Integrin αIIbβ3 that is located on the surface of thrombocytes. The polymorphism of phenylalanin/tyrosine (Y2561F) of vWF was examined with particular attention, as it may increase the rate of arterial embolism due to an increased adhesion rate of thrombocytes. Using a laser scanning microscope, quality and quantity of thrombocyteadhesion could be studied by detecting fluorescent thrombocytes adhered to varying preparations containing the different versions of von Willebrand Factor. In advance, we established certain proof of thrombocyte-mediated adhesion by interaction with the Integrin αIIbβ3 using specific antibodies in our experimental design. In experiments with our subjects‘ blood with the HPA-1a1a allel of Integrin αIIbβ3 we found a higher level of adhesion on immobilised F2561-vWF (wildtype) than on immobilised Y2561-vWF. These results can not support the thesis of Hellermann et al. [9], context to our experiments, stating a correlation between an increased rate of myocardial infarction due to higher risk of arterial embolism in women aged under 55 years carrying the Y2561-vWF variant. Additionally, our experimental results suggest that under higher shear rates of 1000 s-1, as common in coronary arteries, even less thrombocyteadhesion on mutated von Willebrand Factor (Y2561) can be found, not offering an explanation for higher risk of arterial embolism as a basis for myocardial infarction. For the F2561-variant of von Willebrand Factor (in contrast to Y2561-vWF) our experiments showed that increasing shearrates induced a nearly constant degree of thrombocyteadhesion; the experiments therefore demonstrate its preserved physiologic function in haemostasis. | |||||||
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| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Transplantationsdiagnostik und Zelltherapeutika (ITZ) | |||||||
| Dokument erstellt am: | 24.04.2023 | |||||||
| Dateien geändert am: | 24.04.2023 | |||||||
| Promotionsantrag am: | 14.03.2022 | |||||||
| Datum der Promotion: | 04.04.2023 |
