Renin-Angiotensin System and Genetic Factors in Aneurysms

228 Pages·2016·33.77 MB·English

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LUUK TE RIET
Renin-Angiotensin System
and Genetic Factors in Aneurysms
A TRANSLATIONAL APPROACH
LUUK TE RIET
Colofon
L. te Riet
Renin-Angiotensin System and Genetic Factors in Aneurysms: A Translational Approach
ISBN: 978-94-6328-023-5
Cover: Maureen Oude Avenhuis - ([email protected])
Lay-out and chapter design: Luuk te Riet and Maureen Oude Avenhuis
Printed by : CPI Koninklijke Wöhrman B.V.
Copyright © Luuk te Riet 2016
All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system of any nature,
or transmitted in any form or means, without written permission of the author, or when appropriate,
of the publishers of the publications.
Renin-Angiotensin System
and Genetic Factors in Aneurysms
A TRANSLATIONAL APPROACH
Renine-angiotensine systeem
en genetische factoren in aneurysmata:
een translationele aanpak
Proefschrift
Ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de rector magnificus
Prof.dr. H.A.P. Pols
en volgens besluit van het College voor Promoties
De openbare verdediging zal plaatsvinden op
dinsdag 5 april 2016 om 15.30 uur
door
Luuk te Riet
Geboren te Oldenzaal
Promotiecommissie
Promotoren: Prof.dr. A.H.J. Danser
Prof.dr. H.J.M. Verhagen
Overige leden: Prof.dr. J.W. Roos-Hesselink
Prof.dr. D.J.G.M. Duncker
Prof.dr. M.C. de Ruiter
Copromotoren: Dr. J. Essers
Dr. E.V. Rouwet
Voor mijn familie

Table of Contents
Part I
Chapter 1 Introduction: The Renin-Angiotensin Aldosterone Alterations and its Involvement in
Vascular Disease
Chapter 2 Scope of this Thesis
Part II The Role of the Renin-Angiotensin System on Aortic and Cardiac Pathology in
Aneurysmatic Fibulin-4 Mice
Chapter 3 Impaired vascular contractility and aortic wall degeneration in fibulin-4 deficient mice:
effect of angiotensin II type 1 (AT) receptor blockade
1
Chapter 4 Reduced Fibulin-4 Expression Causes Myocardial Remodeling and Dysfunction
Chapter 5 AT Receptor Blockade, but not Renin Inhibition, Reduces Aneurysm Growth and
1
Cardiac Failure in Fibulin-4 Mice
Chapter 6 Fibulin-4 Deficiency Increases TGFβ Signaling in Isolated Aortic Smooth Muscle Cells
Due to Elevated TGFβ2 Levels
Part III The Identification of Genetic Factors Involved in Aneurysms
Chapter 7 RNA Expression Profiling of Abdominal Aortic Aneurysm Disease Identifies Signaling
Cross-talk Between TGFβ and BMP
Chapter 8 Long range polymerase chain reaction amplification of Aortic Aneurysm Genes
Part IV (Pro)Renin Receptor Inhibition in Diabetic Rats
Chapter 9 Deterioration of Kidney Function by the (Pro)renin Receptor Blocker Handle Region
Peptide in Aliskiren-treated Diabetic Transgenic (mRen2)27 Rats
Part V Summary
Chapter 10 Summary and Discussion
Nederlandse samenvatting
Curriculum Vitae
Publications
PhD Portfolio
Dankwoord

CHAPTER I
Part I: Introduction
Renin-Angiotensin-Aldosterone System Alterations
and its Involvment in Vascular Disease
ADAPTED FROM
Te Riet L. et al. Hypertension: renin-angiotensin-aldosterone system
alterations. Circulation Research. 2015 Mar 13; 116(6): 960-975.
Van Thiel BS. et al. The renin-angiotensin system and its involvement
in vascular disease. European Journal of Pharmacology. 2015 Sep 15;
763(Pt A): 3-14.