Role of Coagulation factor XII in atherosclerosis: = Rolle des Koagulationsfaktors XII in der Atherosklerose
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English German |
| Veröffentlicht: |
Würzburg
2014
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| Schlagworte: | |
| Online-Zugang: | Volltext Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | Veröffentlicht 2017 |
| Beschreibung: | 156 Blätter Illustrationen 30 cm |
Internformat
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| 245 | 1 | 0 | |a Role of Coagulation factor XII in atherosclerosis |b = Rolle des Koagulationsfaktors XII in der Atherosklerose |c submitted by Miriam Koch from Freudenstadt |
| 246 | 1 | 1 | |a Rolle des Koagulationsfaktors XII in der Atherosklerose |
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Datensatz im Suchindex
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| adam_text | ROLE OF COAGULATION FACTOR XII IN ATHEROSCLEROSIS
ROLLE DES KOAGULATIONSFAKTORS XII IN DER ATHEROSKLEROSE
DOCTORAL THESIS FOR A DOCTORAL DEGREE
AT THE GRADUATE SCHOOL OF LIFE SCIENCES
JULIUS-MAXIMILIANS-UNIVERSITAET WUERZBURG
SECTION BIOMEDICINE
SUBMITTED BY
MIRIAM KOCH
FROM
FREUDENSTADT
WUERZBURG, 2014
TABLE OF CONTENTS
1 SUMMARY/ZUSAMMENFASSUNG
1.1 SUMMARY 9
1.2 ZUSAMMENFASSUNG 11
INDEX OF ABBREVIATIONS 13
2 INTRODUCTION 20
2.1 ATHEROSCLEROSIS 20
2.1.1 ATHEROSCLEROSIS - AN IMMUNE DISEASE 22
2.1.2 THE INNATE IMMUNE SYSTEM IN ATHEROSCLEROSIS 22
2.1.2.1 MONOCYTES 22
2.1.2.2 MACROPHAGES 23
2.1.2.3 DENDRITIC CELLS (DCS) 26
2.1.3 THE ADAPTIVE IMMUNE SYSTEM IN ATHEROSCLEROSIS 30
2.1.3.1 TH1 CELLS 31
2.1.3.2TH2 CELLS 32
2.1.3.3 TH17 CELLS 32
2.1.3.4 REGULATORY T CELLS (TREGS) 33
2.1.4 THE HAEMOSTATIC SYSTEM IN ATHEROSCLEROSIS 34
2.1.4.1 TISSUE FACTOR (TF) 34
2.1.4.2 FACTOR X (FX) 35
2.1.4.3 FACTOR XI (FXI) 35
2.1.4.4 FACTOR VIII (FVIII) 35
2.1.4.5 THROMBIN 36
37
38
2.1.4.6 PLATELETS
2.1.4.7 TISSUE FACTOR PATHWAY INHIBITOR (TFPI)
2.1.4.8 HYPERCOAGULABILITY MODELS
39
2.1.4.9 FIBRINOLYSIS 39
2.2 COAGULATION FACTOR XII (HAGEMAN FACTOR, FXII) 40
2.2.1 BLOOD COAGULATION PATHWAYS 40
2.2.2 FACTOR XII 41
2.2.2.1 ACTIVATION OF FXII 42
2.2.2 2 IN VIVO INHIBITORS OF FXII ACTIVITY 43
2.2.3 FUNCTIONS OF FXII 43
2.2.3.1 COAGULATION AND KALLIKREIN-KININ-PATHWAY 43
2.2.3.2 FIBRINOLYSIS 44
2.2.3.3 FXII AS A GROWTH FACTOR 44
2.2.3.4 FXII IN ANGIOGENESIS 44
2.2.3.5 FXII IN HEMOSTASIS AND THROMBOSIS 45
2.2.4 FXII IN INFLAMMATION - AND OVERVIEW ABOUT HOW FXII MAY INFLUENCE
47
ATHEROGENESIS
2.2.4.1 FXII IN INFLAMMATORY DISEASES 47
2.2.4.2 INTERACTIONS OF FXII WITH IMMUNE CELLS 47
2.2.4.3 FXII AND THE COMPLEMENT SYSTEM 48
2.2.4 4 INFLAMMATORY FUNCTIONS OF DOWNSTREAM MEDIATORS OF FXII 49
2.2.4.5 FXII MODULATED FIBRINOLYTIC FACTORS IN INFLAMMATION 50
2.2.5 FXII IN ATHEROSCLEROSIS 53
2.3 AIM OF THIS PROJECT 55
3 MATERIAL AND METHODS 56
3.1 MATERIAL 56
3.1.1 CONSUMABLES AND TECHNICAL INSTRUMENTS 56
3.1.1.1 CONSUMABLES 56
3.1.1.2 TECHNICAL INSTRUMENTS 57
3.1.2 KITS AND REAGENTS 59
3.1.2.1 KITS 59
3.1.2.2 CELL CULTURE REAGENTS 59
3.1.2.3 MOLECULAR BIOLOGY REAGENTS 60
3.1.3 CHEMICALS 61
3.1.4 CYTOKINES AND GROWTH FACTORS 62
3.1.5 ANTIBODIES 63
3.1.5.1 CONJUGATED ANTIBODIES 63
3.1.5.2 UNCONJUGATED PRIMARY ANTIBODIES 65
3.1.5.3 CONJUGATED SECONDARY ANTIBODIES 65
3.1.6 PRIMERS 65
3.1.6.1 PRIMERS FOR QPCR 65
3.1.6.2 PRIMERS FOR GENOTYPING PCR 67
3.1.7 ANIMALS 67
3.1.8 MEDIA, BUFFERS AND SOLUTIONS 68
3.1.8.1 MEDIA 68
3.1.8.2 BUFFERS 69
3.1.8.3 SOLUTIONS 71
3.2 METHODS 73
3.2.1 ANIMAL WORK 73
3.2.1.1 MICE AND BREEDING 73
3.2.1.2 SACRIFICE OF MICE AND ORGAN HARVEST 73
3.2.1.3 ORGAN PROCESSING FOR FLOW CYTOMETRY 74
3.2.1.4 PREPARATION OF SERUM AND PLASMA SAMPLES 74
3.2.2 ASSAYS 75
3.2.2.1 BLOOD CHOLESTEROL AND TRIGLYCERIDE MEASUREMENTS 75
3.2.2 2 ELISA 75
3.2.3 FLOW CYTOMETRY 76
3.2.3.1 SURFACE STAINING 76
3.2.3.2 INTRACELLULAR STAINING 76
3.2.4 HISTOLOGY 77
3.2.4.1 EN FACE PREPARATION OF AORTAS 77
3.2.4 2 PREPARATION OF AORTIC ROOTS 78
3.2.4.3 DEPARAFFINIZATION AND REHYDRATION 79
3.2.4 4 ANTIGEN RETRIEVAL 79
3.2.4.5 OIL-RED-O LIPID STAINING FOR AORTAS AND AORTIC ROOT SECTIONS 80
3.2.4 6 COLLAGEN/ELASTIN STAINING OF AORTIC ROOT SECTIONS 80
3.2.4 7 T CELL STAINING OF AORTIC ROOT SECTIONS 80
3.2.4.8 MACROPHAGE (MAC) AND SMOOTH MUSCLE CELL (SMC) 81
STAINING OF AORTIC ROOT SECTIONS
3.2.4.9 ANALYSIS OF PLAQUE AREA IN THE AORTA AND AORTIC ROOT 81
3.2.4.10 ANALYSIS OF NECROTIC CORE AREA, SMC, MAC, T CELL 82
AND COLLAGEN CONTENT IN AORTIC ROOT PLAQUES
3.2.5 CELL CULTURE METHODS 82
3.2.5.1 BONE MARROW-DERIVED DENDRITIC CELL (BMDC) CULTURE 82
3.2.5.2 GENERATION OF L929-CONDITIONED MEDIUM 83
3.2.5.3 BONE MARROW-DERIVED MACROPHAGE (BMM) CULTURE 83
3.2.5.4 ANTIGEN-SPECIFIC T-CELL PROLIFERATION AND POLARIZATION 84
3.2.5.5 ANTIGEN INDEPENDENT T-CELL POLARIZATION 85
3.2.6 NUCLEIC ACID PREPARATION AND VISUALIZATION 85
3.2.6.1 PREPARATION OF TISSUES FOR RNA ISOLATION 85
3.2.6 2 RNA ISOLATION 85
3.2.6.3 REVERSE TRANSCRIPTION (RT) AND QUANTITATIVE REAL-TIME 86
PCR (QPCR)
3.2.6.4 ISOLATION OF GENOMIC TAIL DNA 66
3.2.6.5 GENOTYPING PCR 87
3.2.7 DATA ANALYSIS 88
4 RESULTS 89
4.1 ANALYSIS OF ATHEROSCLEROTIC LESION PROGRESSION IN APOTA MICE 89
DEFICIENT IN FXII
4.1.1 GENERAL CHARACTERIZATION 89
4.1.2 PLAQUE CHARACTERIZATION 90
4.1.3 ANALYSIS OF THE IMMUNOLOGICAL PHENOTYPE IN APOF7 MICE 93
DEFICIENT IN FXII
4.2 ANALYSIS OF MICE DEFICIENT IN FXII UNDER NON-INFLAMMATORY, 99
HOMEOSTATIC CONDITIONS
4.2.1 GENERAL CHARACTERIZATION 99
4.2.2 ANALYSIS OF THE IMMUNOLOGICAL PHENOTYPE OF MICE DEFICIENT 101
IN FXII
4.3 ANALYSIS OF DIRECT FXII INFLUENCES ON DCS, T CELLS OR MACROPHAGES
103
4.4 ANALYSIS OF CHANGES IN FXII MODULATED PATHWAYS 106
4.5 INVESTIGATING THE ROLE OF C5A IN DC-MEDIATED T CELL RESPONSES 107
4.6 ANALYSIS OF IL-12 LEVELS AND OTHER SELECTED CYTOKINES IN
APOEA MICE 112
DEFICIENT IN FXII
4.7 ANALYSIS OF THE MACROPHAGE POLARIZATION STATE IN A P O E MICE 114
DEFICIENT IN FXII
5 DISCUSSION 116
6 REFERENCES 129
7 ACKNOWLEDGEMENTS 151
8 PUBLICATIONS 153
154
9 CURRICULUM VITAE
10 AFFIDAVIT/ EIDESSTATTLICHE ERKLAERUNG 156
|
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| spelling | Koch, Miriam 1981- Verfasser (DE-588)1132829771 aut Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose submitted by Miriam Koch from Freudenstadt Rolle des Koagulationsfaktors XII in der Atherosklerose Würzburg 2014 156 Blätter Illustrationen 30 cm txt rdacontent n rdamedia nc rdacarrier Veröffentlicht 2017 Dissertation Julius-Maximilians-Universität Würzburg 2014 Zusammenfassung in deutscher und englischer Sprache Arteriosklerose (DE-588)4068866-5 gnd rswk-swf Gerinnungsfaktor XII (DE-588)4156840-0 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Arteriosklerose (DE-588)4068866-5 s Gerinnungsfaktor XII (DE-588)4156840-0 s DE-604 Erscheint auch als Online-Ausgabe, PDF urn:nbn:de:bvb:20-opus-97850 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-97850 Resolving-System kostenfrei Volltext B:DE-101 application/pdf http://d-nb.info/1132589533/04 Resolving-System Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029742722&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Koch, Miriam 1981- Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose Arteriosklerose (DE-588)4068866-5 gnd Gerinnungsfaktor XII (DE-588)4156840-0 gnd |
| subject_GND | (DE-588)4068866-5 (DE-588)4156840-0 (DE-588)4113937-9 |
| title | Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose |
| title_alt | Rolle des Koagulationsfaktors XII in der Atherosklerose |
| title_auth | Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose |
| title_exact_search | Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose |
| title_full | Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose submitted by Miriam Koch from Freudenstadt |
| title_fullStr | Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose submitted by Miriam Koch from Freudenstadt |
| title_full_unstemmed | Role of Coagulation factor XII in atherosclerosis = Rolle des Koagulationsfaktors XII in der Atherosklerose submitted by Miriam Koch from Freudenstadt |
| title_short | Role of Coagulation factor XII in atherosclerosis |
| title_sort | role of coagulation factor xii in atherosclerosis rolle des koagulationsfaktors xii in der atherosklerose |
| title_sub | = Rolle des Koagulationsfaktors XII in der Atherosklerose |
| topic | Arteriosklerose (DE-588)4068866-5 gnd Gerinnungsfaktor XII (DE-588)4156840-0 gnd |
| topic_facet | Arteriosklerose Gerinnungsfaktor XII Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-97850 http://d-nb.info/1132589533/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029742722&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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