Influence of blood flow on shear stress responsive genes in the
development of cardiac malformations : The involvement of the
endothelin-1 pathway
Groenendijk, B.C.W.
Citation
Groenendijk, B. C. W. (2006, March 23). Influence of blood flow on shear stress responsive
genes in the development of cardiac malformations : The involvement of the endothelin-1
pathway. Retrieved from https://hdl.handle.net/1887/4346
Version:
Corrected Publisher’s Version
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Licence agreement concerning inclusion of doctoral thesis in the
Institutional Repository of the University of Leiden
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Influence of Blood Flow on Shear Stress Responsive Genes
in the Development of Cardiac Malformations
The Involvement of the Endothelin-1 Pathway
Invloed van Bloedstroom op Shear Stress Responsieve Genen
in de Ontwikkeling van Hartafwijkingen.
Colofon
Cover Images: 3-dimensional lumen reconstruction of a HH18 (3 days of incubation) chicken embryonic heart showing KLF2 expression, a high shear stress marker, in blue (Chapter 2).
Influence of Blood Flow on Shear Stress Responsive Genes in the Development of Cardiac Malformations. The involvement of the Endothelin-1 Pathway
Bianca Christina Woutrina Groenendijk
Thesis Leiden University – With Ref. – With summary in Dutch
Copyright © 2006, B.C.W. Groenendijk
All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, either electronical, mechanical, by photocopy, recording or otherwise, without prior written permission from the author.
ISBN: 90-8559-108-2
Influence of Blood Flow on Shear Stress Responsive Genes
in the Development of Cardiac Malformations
The Involvement of the Endothelin-1 Pathway
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus Dr. D.D. Breimer,
hoogleraar in de faculteit der Wiskunde en
Natuurwetenschappen en die der Geneeskunde,
volgens besluit van het College voor Promoties
te verdedigen op donderdag 23 maart 2006
klokke 15:15 uur
door
Bianca Christina Woutrina Groenendijk
Promotiecommissie
Promotores:
Prof. dr. R.E. Poelmann
Prof. dr. J.W. Wladimiroff (Erasmus Medisch Centrum)
Copromotor:
Dr. B.P. Hierck
Referent:
Prof. dr. A. van der Laarse
Lid:
Dr. R. Krams (Erasmus Medisch Centrum)
The study described in this thesis was carried out at the Department of Anatomy and
Embryology of the Leiden University Medical Centre and was supported by a grant of the
Netherlands Heart Foundation (NHF-2000.016).
Financial support by the Netherlands Heart Foundation for the publication of this thesis is
gratefully acknowledged.
Breek de dag, tik een eitje
Contents
Chapter 1. General Introduction 9
1.1 Hemodynamics and Cardiac Development 10
1.1.1 Fluid Dynamics 10
1.1.2 Cardiac Development 11 1.1.3 Cardiac Malformations 12 1.1.4 Blood Flow in the Chicken Embryo 13
1.1.5 Venous Clip Model 14
1.2 Shear Stress and Gene Expression 14
1.2.1 Shear Sensing 14
1.2.2 Gene Expression 15
1.3 Setting of this Thesis 17
1.4 Chapter Outline 18
1.5 References 19
Chapter 2. Development-related Changes in the Expression of Shear Stress 25 Responsive Genes KLF2, ET-1, and NOS-3 in the Developing
Cardiovascular System of Chicken Embryos. Dev Dyn 230(1):57-68, 2004
Chapter 3. Changes in Shear Stress-related Gene Expression After 47 Experimentally Altered Venous Return in the Chicken Embryo.
Circ Res 96(12):1291-1298, 2005
Chapter 4. Components of the Endothelin Pathway Play a Role in the 69 Development of Cardiovascular Defects in the Chicken Venous
Clip Model.
Chapter 5. Differential Effects of Endothelin-1 and Endothelin Receptor 91 Antagonists on Chicken Yolk Sac and Embryonic Hemodynamics.
Chapter 6. Monocilia on Chicken Embryonic Endocardium in Low Shear Stress 111 Areas.
Dev Dyn 235(1):19-28, 2006
Chapter 7. General Discussion 131
7.1 Influence of Blood Flow on Gene Expression 132 7.1.1 Gene Expression and Shear Stress 132
7.1.2 Shear Sensing 133
7.2 Mechanism of the ET-1 Pathway in the Venous Clip Model 135 7.2.1 ET-1 in Cushion Development 137 7.2.2 ET-1 in the Cardiac Wall 138 7.2.3 ET-1 in Cardiac Function and Morphology 139 7.2.4 Other Mechanisms Involved in Venous Clip 141
