The fetal origin of adult atherosclerosis : a study in ApoE and Ldlr mouse models

The fetal origin of adult atherosclerosis : a study in ApoE and Ldlr mouse models

Alkemade, F.E.

Citation

Alkemade, F. E. (2009, April 15). The fetal origin of adult atherosclerosis : a study in ApoE and Ldlr mouse models. Retrieved from https://hdl.handle.net/1887/13727

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

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The Fetal Origin of Adult Atherosclerosis

A Study in ApoE and Ldlr Mouse Models

Fanneke Elizabeth Alkemade

Colofon

Cover: Water drops on a fresh shoot Layout cover: Wouter Alkemade

The Fetal Origin of Adult Atherosclerosis A Study in ApoE and Ldlr Mouse Models Fanneke Elizabeth Alkemade

Thesis Leiden University Medical Center

© 2009 Fanneke Elizabeth Alkemade, Leiden, The Netherlands

All rights reserved. No part of this book may be reproduced or transmitted, in any form or by any means, without written permission of the author.

ISBN 978-90-9023927-9

Printed by Gildeprint Drukkerijen B.V.

The Fetal Origin of Adult Atherosclerosis

A Study in ApoE and Ldlr Mouse Models

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus Prof. Mr. P.F. van der Heijden, volgens besluit van het College voor promoties

te verdedigen op woensdag 15 april 2009 klokke 13.45 uur

door

Fanneke Elizabeth Alkemade

geboren te Leiden in 1981

Promotiecommissie

Promotores Prof. Dr. A.C. Gittenberger-de Groot

Prof. Dr. L.M. Havekes

Co-promotores Dr. M.C. de Ruiter

Dr. K. Willems van Dijk

Overige leden Prof. Dr. P.J. van den Elsen

Prof. Dr. C.J.M. de Vries (Universiteit van Amsterdam) Prof. Dr. J. Waltenberger (Universiteit Maastricht)

The research presented in this thesis was performed at the Department of Anatomy and Embryology of the Leiden University Medical Center and was supported by a grant of the Netherlands Heart Foundation (2003B241).

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

Additional financial support is generously provided by the “J.E. Jurriaanse Stichting”.

The pessimist sees difficulty in every opportunity.

The optimist sees the opportunity in every difficulty.

- Sir Winston Churchill -

Voor mijn ouders

Contents

Chapter 1

General Introduction

9

Chapter 2

Intrauterine Exposure to Maternal Atherosclerotic Risk

19

Factors Increases the Susceptibility to Atherosclerosis

in Adult Life

Arterioscler Thromb Vasc Biol 2007;27:2228-2235

Chapter 3

Maternal ApoE-Deficiency Promotes Collar-Induced

41

Neointima Formation in Adult ApoE^+/- Offspring Even

Without Cholesterol Feeding Submitted for publication

Chapter 4

The Effect of Maternal Hypercholesterolemia as a

57

Consequence of LDL Receptor-Deficiency on Vascular

Lesion Formation in the Offspring Submitted for publication

Chapter 5

Endothelial-to-Mesenchymal-Transformation during the

75

Initial Stages of Neointima Formation

Submitted for publication

Chapter 6

Maternal Transmission of Risk for Atherosclerosis

93

Curr Opin Lipidol 2008;19:333-337

Chapter 7

Altered Global Histone Methylation Profiles in Vascular

105

Endothelial and Smooth Muscle Cells in Offspring Exposed to Maternal Apolipoprotein E-Deficiency Submitted for publication

Chapter 8

General Discussion

127

Summary

145

Samenvatting

149

Curriculum Vitae

155

Acknowledgements

157

List of Publications

159