University of Groningen
Molecular mechanisms of Endothelial-Mesenchymal Transition in coronary artery stenosis
and cardiac fibrosis
Vanchin, Byambasuren
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2018
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Vanchin, B. (2018). Molecular mechanisms of Endothelial-Mesenchymal Transition in coronary artery stenosis and cardiac fibrosis. University of Groningen.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
Molecular mechanisms of
Endothelial-Mesenchymal Transition in
coronary artery stenosis
and cardiac ibrosis
Byambasuren Vanchin
2018
The research described in this thesis was performed at the Cardiovascular Regenerative Medicine laboratory at the Department of Pathology and Medical Biology in University Medical Center Groningen. The work was funded by Mongolian State Training Fund and Groningen University Institute for Drug Exploration (GUIDE), Graduate School of Medical Sciences.
The author gratefully acknowledges the inancial support for printing of this thesis by: The Graduate School of Medical Sciences and Centre for East Asian Studies Groningen (CEASG).
ISBN: 978-94-034-0756-2 (printer version)
ISBN: 978-94-034-0755-5 (digital version)
Front cover design: Viktoriia Starokozhko & Byambasuren Vanchin Layout design: Byambasuren Vanchin
Printed by: Gildeprint, Enschede, The Netherlands
© Copyright 2018 Byambasuren Vanchin
All right reserved. No parts of this publication may be reproduced, stored on retrieval system, or transmitted in any form or by any means, without the permission of the author.
Molecular mechanisms of
Endothelial-Mesenchymal Transition
in coronary artery stenosis and
cardiac ibrosis
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magniicus Prof. E. Sterken
and in accordance with the decision by the College of Deans. This thesis will be defended in public on
Tuesday 26 June 2018 at 09.00 hours
by
Byambasuren Vanchin
born on 13 December 1986 in Ulaanbaatar, Mongolia
Supervisor
Prof. M.C. Harmsen
Co-supervisor
Dr. G. Krenning
Assessment Committee
Prof. J.L. Hillebrands
Prof. M.J.T.H. Goumans
Prof. E.M. Zeisberg
Paranymphs
Maroesjka Spiekman
Marloes Sol
6
CONTENTS
CONTENTS
CHAPTER 1. INTRODUCTION AND AIM OF THIS THESIS 7
CHAPTER 2. PLEIOTROPIC TREATMENT OF PRO-ATHEROGENIC ENDOTHELIUM: ARE SIRT1 AND EZH2 PROMISING CANDIDATES? 21
CHAPTER 3. MICRORNA-374B INDUCES ENDOTHELIAL-TO-MESENCHYMAL TRANSITION AND NEOINTIMA FORMATION THROUGH THE INHIBITION OF MAPK7 SIGNALING 43
CHAPTER 4. THE DECREASE IN HISTONE METHYLTRANSFERASE EZH2 IN RESPONSE TO FLUID SHEAR STRESS ALTERS ENDOTHELIAL GENE EXPRESSION AND PROMOTES QUIESCEN CE 75
CHAPTER 5. RECIPROCAL REGULATION OF ENDOTHELIAL-MESENCHYMAL TRANSITION BY MAPK7 AND EZH2 ACTIVITY IN INTIMAL HYPERPLASIA AND CORONARY ARTERY DISEASE 107 CHAPTER 6. INTRACELLULAR GALECTIN-3 FACILITATES TGFΒ-INDUCED ENDOTHELIAL-MES-ENCHYMAL TRANSITION 129
CHAPTER 7. RESEARCH SUMMARY 143
CHAPTER 8. EPILOGUE 153
CHAPTER 9. NEDERLANDSE SAMENVATTING 161
