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Cover Page The handle http://hdl.handle.net/1887/29594 holds various files of this Leiden University dissertation

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Cover Page

The handle http://hdl.handle.net/1887/29594 holds various files of this Leiden University dissertation

Author: Safdar, Huma

Title: Characterization of mouse coagulation (regulatory) genes with use of RNAi

Issue Date: 2014-11-04

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Characterization of mouse coagulation (regulatory) genes with use of RNAi

Huma Safdar

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Characterization of mouse coagulation (regulatory) genes with use of RNAi

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus prof. dr. mr. C.J.J.M. Stolker volgens besluit van het College voor Promoties

te verdedigen op dinsdag 04 november 2014 klokke 13:45 uur

door

Huma Safdar

Geboren te Lahore, Pakistan

in 1979

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Promotiecommissie

Promotor:

Prof. dr. P.H. Reitsma

Co-promotor:

dr. B.J.M. van Vlijmen

Overige leden:

Prof. dr. S.J.H. van Deventer

Prof. dr. C.J.M. van Vries (University of Amsterdam) Prof. dr. J. Kuiper

The research described in this was financially supported by the Dutch Organisation for Scientific Research (NWO-TOP Grant #40-00812-98-07- 045) and was performed at the Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis of the Leiden University Medical Center in Leiden, the Netherlands.

Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.

Additional support was kindly provided by Life Technologies.

Cover illustration: cross section (hematoxyline/eosin staining) of a mouse liver depleted with protein C and antithrombin.

© 2014 H. Safdar

ISBN: 978-94-6203-662-8

Printed by: CPI Koninklijke Wöhrmann

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If you can dream it, you can do it.

(Walt Disney, 1901-1966)

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Table of contents

Chapter 1 General introduction 9

Chapter 2 The role of hepatocyte nuclear factor 4α in regulating mouse hepatic anticoagulation and fibrinolysis gene transcript levels

39

Chapter 3 Modulation of mouse coagulation gene transcription following acute in vivo delivery of synthetic small interfering RNAs targeting HNF4α and C/EBPα

47

Chapter 4 The Role of FOXA1 in mouse hepatic estrogen receptor α signaling

75

Chapter 5 Acute and severe coagulopathy in adult mice following silencing of hepatic antithrombin and protein C production

101

Chapter 6 Regulation of the F11, Klkb1, Cyp4v3 gene cluster in livers of metabolically challenged mice

113

Chapter 7 General discussion 139

Chapter 8 Summary

Summary in Dutch (Samenvatting)

163

Acknowledgements 175

Curriculum Vitae 181

Publications 183

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