Citation
Loomans, C. J. M. (2007, March 14). Endothelial progenitor cell dysfunction in diabetes
mellitus. Retrieved from https://hdl.handle.net/1887/11410
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the
Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/11410
Note: To cite this publication please use the final published version (if applicable).
Endothelial Progenitor Cell dysfunction in
Diabetes Mellitus
door Cindy J.M. Loomans
Endothelial Progenitor Cell dysfunction in Diabetes Mellitus Cindy J.M. Loomans
Thesis, University of Leiden -with references- including summary in Dutch
ISBN-10: 90-9021526-3 ISBN-13: 978-90-9021526-6
Layout: T. Kwaks
Printed by: Digital Printing Partners Utrecht BV
Cover illustration: "Blind men examining an elephant". Hokusai Magna Series, volume 8 (1818), page 13, 14.
© 2007, Cindy Loomans, Leiden, The Netherlands
All rights reserved. No parts of this thesis may be reproduced or transmitted in any form, by any means, electronic or mechanical, without prior written permission of the author.
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Endothelial Progenitor Cell dysfunction in
Diabetes Mellitus
Proefschrift
ter verkrijging van
de graad Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus prof. mr. P.F. van de Heijden,
volgens besluit van het College voor Promoties
te verdedigen op woensdag 14 maart 2007
klokke 15.00 uur
door
Cindy Johanna Maria Loomans
geboren te Bergeijk
in 1976
Referent: Prof. Dr. J.W. Jukema
Overige leden: Prof. Dr. A.J. Rabelink Prof. Dr. Ir. E.A.L. Biessen
Dr. R. De Crom (Erasmus Universiteit, Rotterdam) Dr. M.C. Verhaar (UMCU, Utrecht)
Prof. Dr. A.C. Gittenberger-de Groot
Financial Support
The study described in this thesis is supported by a grant of the Netherlands Heart Foundation (NHS-2000.019, NHS-2002B157).
Financial support by the Netherlands Heart Foundation and the Dutch Diabetes Foundation for the publication of this thesis is gratefully acknowledged.
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It was men of Indostan To learning much inclined, Who went to see the Elephant (Though all of them were blind),
That each by observation Might satisfy their mind
And so these men of Indostan Disputed loud and long, Each in his own opinion Exceeding stiff and strong, Though each was partly in the right,
And all were in the wrong!
So oft in theologic wars, The disputants, I ween, Rail on in utter ignorance Of what each other mean, And prate about an Elephant
Not one of them has seen!
John Godfrey Saxe (1816-1887)
In memory of my Mom and dedicated to my Dad.
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Contents Page nr.
Chapter 1 General introduction 9
Chapter 2 CD34+ cells home, proliferate and participate in capillary formation, and in combination with CD34- cells enhance
tube formation in a 3-dimensional matrix. 37
Chapter 3 Endothelial progenitor cell dysfunction: A novel concept in the pathogenesis of vascular complications of
type 1 diabetes. 65
Chapter 4 Endothelial progenitor cell dysfunction in type1 Diabetes:
Another consequence of oxidative stress? 81
Chapter 5 Angiogenic murine endothelial progenitor cells are derived from a myeloid bone marrow fraction and can be identified
by endothelial NO sunthase expression. 103
Chapter 6 Endothelial progenitor cell dysfunction in hyperglycemia
originates in myeloid precursor cells in the bone marrow. 131
Chapter 7 The PPAR agonist pioglitazone is a potent transcriptional
trans-repressor in both monocytes and endothelial progenitor cells of
patients with type 2 Diabetes. 155
Chapter 8 Conclusions, general discussion and future directions 177
Chapter 9 Summary / Samenvatting 191
Abbreviations 195
Curriculum Vitae 197
List of publications 199
Dankwoord 201