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The following handle holds various files of this Leiden University dissertation:

http://hdl.handle.net/1887/60912

Author: Bruin, R.G. de

Title: The RNA-binding protein Quaking in vascular health and disease

Issue Date: 2018-04-05

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The RNA-binding protein Quaking in vascular health and disease

R.G. de Bruin

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The RNA-binding protein Quaking in vascular health and disease ISBN: 978-94-028-0944-2

© R.G. de Bruin 2018

© Cover photograph: T.D. Matngelsen, USA, printed with permission

All rights are reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without permission of the copyright owners.

The research presented in this thesis was performed at the Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, The Netherlands.

And the Lady Davis Institute for Medical Research, McGill University, Montréal, Canada.

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The RNA-binding protein Quaking in vascular health and disease

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden

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

te verdedigen op donderdag 5 april 2018 klokke 16.15 uur

door

Ruben Gosewinus de Bruin

geboren te 's-Gravenhage in 1987

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Promotiecommissie

Promotor Prof. dr. A.J. van Zonneveld

Copromotor Dr. E.P. van der Veer

Overige leden Prof. Dr. A.J. Rabelink Prof. Dr. P.H. Reitsma Prof. Dr. D.E. Atsma

Prof. Dr. H. van Esch, Leuven University, Belgium Prof. Dr. S. Richard, McGill University, Canada dr. J.M. van Gils

Financial support:

Medisch Specialistisch Bedrijf van het Groene Hart Ziekenhuis

Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged The cover of this thesis was generously provided by Thomas D. Mangelsen, http://mangelsen.com

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Opgedragen aan Dick Gosewinus de Bruin

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Table of contents

Chapter 1 Preface: English and Dutch summary 9

Chapter 2 Scope of this thesis 13

Chapter 3 Introduction to cardiovascular disease and RNA biology 17

Chapter 4 The RNA-binding protein Quaking 29

Chapter 5 Emerging roles for RNA-binding proteins as effectors and 51

regulators of cardiovascular disease European Heart Journal 2016

Chapter 6 Quaking, an RNA-Binding Protein, Is a Critical Regulator of 77

Vascular Smooth Muscle Cell Phenotype Circulation Research 2013

Chapter 7 Quaking promotes monocyte differentiation into pro- 105

atherogenic macrophages by controlling pre-mRNA splicing and gene expression

Nature Communications 2016

Chapter 8 The RNA-binding protein quaking maintains endothelial 149

barrier function and affects VE-cadherin and β-catenin protein expression.

Scientific Reports 2016

Chapter 9 Targeting Quaking ameliorates macrophage-induced 171

renal interstitial fibrosis and induces alternative splicing of pre-mRNA transcripts in differentiated macrophages Manuscript in preparation

Chapter 10 Discussion & future directions 193

Chapter 11 Appendices 209

Curriculum Vitae Bibliography Dankwoord

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