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Endothelial progenitor cell dysfunction in diabetes mellitus Loomans, C.J.M.

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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).

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Endothelial Progenitor Cell dysfunction in

Diabetes Mellitus

door Cindy J.M. Loomans

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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

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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

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