Proteasome inhibition in experimental right ventricular hypertrophy: a novel therapeutic approach?
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Gießen
VVB Laufersweiler Verlag
2017
|
| Ausgabe: | 1. Auflage |
| Schriftenreihe: | édition scientifique
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 127 Seiten Diagramme, Illustrationen 21 cm x 14.6 cm, 145 g |
| ISBN: | 3835965182 9783835965188 |
Internformat
MARC
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| 049 | |a DE-188 | ||
| 100 | 1 | |a Heitmeier, Tanja |e Verfasser |0 (DE-588)112402591X |4 aut | |
| 245 | 1 | 0 | |a Proteasome inhibition in experimental right ventricular hypertrophy |b a novel therapeutic approach? |c submitted by Tanja Heitmeier |
| 250 | |a 1. Auflage | ||
| 264 | 1 | |a Gießen |b VVB Laufersweiler Verlag |c 2017 | |
| 300 | |a 127 Seiten |b Diagramme, Illustrationen |c 21 cm x 14.6 cm, 145 g | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 0 | |a édition scientifique | |
| 502 | |b Dissertation |c Justus-Liebig-Universität Gießen |d 2016 | ||
| 650 | 7 | |a proteinases |2 cabt | |
| 650 | 7 | |a experiments |2 cabt | |
| 650 | 7 | |a ventricles |2 cabt | |
| 650 | 7 | |a therapy |2 cabt | |
| 650 | 7 | |a hypertrophy |2 cabt | |
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029673159&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-029673159 | ||
Datensatz im Suchindex
| _version_ | 1804177450466279424 |
|---|---|
| adam_text | T
ABLE
OF
CONTENT
SUMMARY............................................................................................................................................
4
ZUSAMMENFASSUNG.............................................................................................................................
5
TABLE OF
CONTENT.................................................................................................................................
7
LIST OF
FIGURES...................................................................................................................................
12
LIST OF
TABLES....................................................................................................................................
13
1
INTRODUCTION.............................................................................................................................
14
1.1 PULMONARY HYPERTENSION AND THE RIGHT
VENTRICLE............................................................14
1.1.1 WHY SHOULD WE CARE ABOUT THE RIGHT VENTRICLE?
........................
16
1.1.2 DIFFERENCES BETWEEN THE RIGHT AND LEFT VENTRICLE
.....................................................
17
1.1.3 RIGHT VENTRICULAR HYPERTROPHY AND FAILURE
..............................................................
19
1.2 THE PROTEASOME AND PROTEASOME
INHIBITION...................................................................22
1.2.1 THE 26S PROTEASOME - FORM AND
FUNCTION................................................................22
1.2.2 THE PROTEASOME IN HEART
DISEASES...........................................................................25
1.2.3 PROTEASOME
INHIBITION..............................................................................................
28
1.3 OBJECTIVE OF THIS
WORK......................................................................................................
29
2 MATERIALS AND
METHODS............................................................................................................
30
2.1
ANIMALS............................................................................................................................
30
2.2 INSTRUMENTS AND
CHEMICALS..............................................................................................
30
2.2.1 PROTEASOME INHIBITORS AND
VEHICLES.........................................................................30
2.3 STUDY
DESIGN.....................................................................................................................
30
2.3.1 SEQUENTIAL
DESIGN.....................................................................................................
31
2.3.2 DRUG
ADMINISTRATION.................................................................................................
32
2.3.3 ANIMAL
GROUPS..........................................................................................................
33
2.4
ECHOCARDIOGRAPHY...........................................................................................................
34
2.4.1
INTRODUCTION.............................................................................................................
34
2.4.2 TIME
POINTS...............................................................................................................34
2.4.3
ANAESTHESIA...............................................................................................................35
2.4.4 PROCEDURE
35
2.4.5 IMAGES AND
PARAMETERS.............................................................................................
36
2.5 PULMONARY ARTERY BANDING
(PAB)...................................................................................
37
2.5.1
INTRODUCTION..............................................................................................................37
2.5.2
PREPARATION...............................................................................................................
38
2.5.3 THE
SURGERY...............................................................................................................
39
2.5.4 POST-OPERATIVE TREATM
ENT.........................................................................................39
2.5.5 SHAM
SURGERY............................................................................................................40
2.6 HEMODYNAMIC
MEASUREMENTS.........................................................................................
40
2.6.1
INTRODUCTION.............................................................................................................
40
2.6.2 INDUCING THE
CATHETER...............................................................................................
40
2.6.3 IMAGES AND
PARAMETERS............................................................................................40
2.7 PROPERTIES OF THE RIGHT
VENTRICLE......................................................................................
41
2.8 TISSUE
PROCESSING............................................................................................................
41
2.9
HISTOLOGY...........................................................................................................................42
2.9.1 PICROSIRIUS RED STAINING DETERMINES COLLAGEN
..........................................................
42
2.9.2 WGA FLUORESCENT STAINING TO ASSES CARDIOMYOCYTE SIZE
..........................................
43
2.9.3 STAINING OF
RPN6........................................................................................................44
2.10 PROTEIN
ANALYSIS................................................................................................................45
2.10.1 PROTEIN
EXTRACTION....................................................................................................
45
2.10.2 PROTEIN
QUANTIFICATION..............................................................................................
46
2.10.3 PROTEASOME ACTIVITY ASSAY (GLO ASSAY)
..........................
46
2.10.4 ACTIVITY BASED PROBES (ABP) AND NATIVE GEL ANALYSIS
..............................................
46
2.10.5 SDS-PAGE AND WESTERN
BLOTTING..............................................................................
47
2.11 MRNA
ANALYSIS.................................................................................................................
48
2.11.1
EXTRACTION.................................................................................................................
48
2.11.2 REVERSE
TRANSCRIPTION...............................................................................................
46
2.11.3 REAL TIME QUANTITATIVE POLYMERASE CHAIN REACTION
.................................................
46
2.12 STATISTICAL
ANALYSIS............................................................................................................48
3 RESULTS,
49
3.1 RESULTS PART A: DEVELOPMENT OF RIGHT VENTRICULAR HYPERTROPHY WAS
ASSOCIATED WITH
PROTEASOME
ACTIVATION.................................................................................................................
49
3.1.1 PULMONARY ARTERY BANDING INDUCED RIGHT VENTRICULAR HYPERTROPHY
.......................
49
3.1.2 DETERIORATION OF RIGHT VENTRICULAR FUNCTION AND STRUCTURE
......................................
50
3.1.3 HEMODYNAMIC ADAPTION TO INCREASED
RESISTANCE.....................................................51
3.1.4 INCREASE OF CARDIOMYOCYTE SIZE AND COLLAGEN CONTENT
.............................................
52
3.1.5 PROTEASOME CATALYTIC ACTIVITY INCREASED IN RIGHT VENTRICULAR
HYPERTROPHY
.............
53
3.1.6 268 PROTEASOME AUGMENTATION IN RIGHT VENTRICULAR HYPERTROPHY
..........................
54
3.1.7 RPN6 UPREGULATION IN RIGHT VENTRICULAR HYPERTROPHY
..............................................
56
3.2 RESULTS PART B: EFFECTS OF PREVENTIVE PROTEASOME INHIBITION IN RIGHT
VENTRICULAR
HYPERTROPHY.................................................................................................................................
58
3.2.1 RIGHT VENTRICULAR MASS REMAINED UNCHANGED
.........................................................
58
3.2.2 FUNCTION AND STRUCTURE OF THE RIGHT VENTRICLE UNDER PREVENTIVE
PROTEASOME
INHIBITION..................................................................................................................................59
3.2.3 PHYSIOLOGICAL BLOOD PRESSURE AFTER PREVENTIVE PROTEASOME
INHIBITION
..................
61
3.2.4 EFFECTS OF PREVENTIVE TREATMENT ON CARDIOMYOCYTE SIZE AND COLLAGEN
CONTENT
.......
63
3.2.5 PROTEASOME ACTIVITY IN THE CONTEXT OF PREVENTIVE TREATM ENT
..................................
65
3.3 RESULTS PART C: THERAPEUTIC PROTEASOME INHIBITION REVEALED
DIFFERENCES BETWEEN EFFECTS
OF BTZ AND
ONX...........................................................................................................................
65
3.3.1 AFTER PAB SURGERY, RIGHT VENTRICULAR HYPERTROPHY DEVELOPED WITHIN
ONE WEEK
.....
65
3.3.2 ONX REDUCED RIGHT VENTRICULAR
MASS........................................................................66
3.3.3 THERAPEUTIC PROTEASOME INHIBITION IMPROVED RIGHT VENTRICULAR
HYPERTROPHY
......
67
3.3.4 EFFECTS OF THERAPEUTIC PROTEASOME INHIBITION ON HEMODYNAMICS
...........................
66
3.3.5 ONX DECREASED CARDIOMYOCYTE AND COLLAGEN CONTENT
.............................................
71
3.3.6 THERAPEUTIC PROTEASOME INHIBITION DECREASED 20S COMPLEX AND ITS
ACTIVITY
.........
73
3.4 RESULTS PART D: RPN6 INCREASED IN RIGHT VENTRICULAR HYPERTROPHY
.................................
74
3.4.1 RPN6 INCREASED IN HYPERTROPHIED RIGHT VENTRICULAR TISSUE OF
MICE.........................74
3.4.2 EXPRESSION OF RPN6 IN HYPERTROPHIED RIGHT VENTRICULAR TISSUE OF
HUMANS
.............
75
4
DISCUSSION................................................................................................................................
77
4.1 3-WEEK-PAB MODEL: HYPERTROPHY, BUT NO FAILURE OF THE RIGHT
VENTRICLE...........................77
4.1.1 PAB HAS AN ACUTE IMPACT ON THE RIGHT VENTRICLE
.......................................................
77
4.1.2 STAGING OF
PAB...........................................................................................................
77
4.1.3 MONITORING CLINICAL
SYMPTOMS..................................................................................78
4.2 PROTEASOME ACTIVITY INCREASED IN RIGHT VENTRICULAR HYPERTROPHY
...................................
80
4.3 PROTEASOME INHIBITION IN HEART HYPERTROPHY
..................................................................
81
4.3.1 BTZ AND ONX- DIFFERENT COMPOUNDS, DIFFERENT EFFECTS
.............................................
62
4.3.2 EXAMPLES FOR POSSIBLE MECHANISMS
.........................................................................
63
4.3.3 POSSIBLE SIDE
EFFECTS.................................................................................................
85
4.4 RPN6- A NEW THERAPEUTIC
TARGET?.....................................................................................
86
4.4.1 268 INCREASED IN EXPERIMENTAL RIGHT VENTRICULAR HYPERTROPHY
...............................
66
4.4.2 RPN6 MAY HELP TO TARGET PROTEIN DEGRADATION BY 268
.............................................
67
4.5
CONCLUSION........................................................................................................................89
5
SUPPLEMENT..............................................................................................................................
90
5.1 INSTRUMENTS, CHEMICALS AND
REAGENTS..............................................................................
90
5.1.1
ANTIBODIES.................................................................................................................90
5.1.2 BUFFERS AND
SOLUTIONS................................................................................................91
5.1.3
CHEMICALS..................................................................................................................
95
5.1.4
CONSUMABLES............................................................................................................
97
5.1.5
ENZYMES....................................................................................................................96
5.1.6 HUMAN RIGHT VENTRICULAR
TISSUE................................................................................99
5.1.7 LABORATORY EQUIPMENT AND
SOFTWARE.......................................................................
99
5.1.8 PRIMER, KITS AND
STANDARDS.....................................................................................
101
5.1.9 SURGICAL
EQUIPMENT.................................................................................................
102
5.2 ADDITIONAL
TABLES............................................................................................................
104
5.2.1 SCORE
SHEET..............................................................................................................104
5.2.2 LIST OF
ABBREVIATIONS...............................................................................................106
6
REFERENCES..............................................................................................................................I
L L
PUBLICATIONS...................................................................................................................................
125
DECLARATION.................................................................................................
.
....
.
...........................
126
ACKNOWLEDGEMENTS
...................................................................................................................127
|
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| id | DE-604.BV044268469 |
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| indexdate | 2024-07-10T07:48:16Z |
| institution | BVB |
| isbn | 3835965182 9783835965188 |
| language | English |
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| physical | 127 Seiten Diagramme, Illustrationen 21 cm x 14.6 cm, 145 g |
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| spelling | Heitmeier, Tanja Verfasser (DE-588)112402591X aut Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? submitted by Tanja Heitmeier 1. Auflage Gießen VVB Laufersweiler Verlag 2017 127 Seiten Diagramme, Illustrationen 21 cm x 14.6 cm, 145 g txt rdacontent n rdamedia nc rdacarrier édition scientifique Dissertation Justus-Liebig-Universität Gießen 2016 proteinases cabt experiments cabt ventricles cabt therapy cabt hypertrophy cabt (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029673159&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Heitmeier, Tanja Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? proteinases cabt experiments cabt ventricles cabt therapy cabt hypertrophy cabt |
| subject_GND | (DE-588)4113937-9 |
| title | Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? |
| title_auth | Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? |
| title_exact_search | Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? |
| title_full | Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? submitted by Tanja Heitmeier |
| title_fullStr | Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? submitted by Tanja Heitmeier |
| title_full_unstemmed | Proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach? submitted by Tanja Heitmeier |
| title_short | Proteasome inhibition in experimental right ventricular hypertrophy |
| title_sort | proteasome inhibition in experimental right ventricular hypertrophy a novel therapeutic approach |
| title_sub | a novel therapeutic approach? |
| topic | proteinases cabt experiments cabt ventricles cabt therapy cabt hypertrophy cabt |
| topic_facet | proteinases experiments ventricles therapy hypertrophy Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029673159&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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