University of Groningen Novel heart failure biomarkers Du, Weijie

University of Groningen

Novel heart failure biomarkers

Du, Weijie

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2019

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Du, W. (2019). Novel heart failure biomarkers: Physiological studies to understand their complexity.

University of Groningen.

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Novel Heart Failure Biomarkers：

Physiological studies to understand their complexity

Financial support by the Dutch Heart Foundation for the publication of this thesis is

gratefully acknowledged.

Financial support by the Groningen University institute for Drug Exploration (Guide) and the

Rijksuniversiteit Groningen for publication of this thesis is gratefully acknowledged.

Financial support by Natural Science Foundation of China for publication of this thesis is

gratefully acknowledged.

Novel Heart Failure Biomarkers: Physiological studies to understand their complexity © copyright 2019 Weijie Du

All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without permission of the author.

ISBN: 978-94-034-1386-0; printed version ISBN: 978-94-034-1387-7; electronic version Layout: Weijie Du

Novel Heart Failure Biomarkers

Physiological studies to understand their complexity

PhD thesis

to obtain the degree of PhD at the

University of Groningen

on the authority of the

Rector Magnificus prof. E. Sterken

and in accordance with

the decision by the College of Deans.

This thesis will be defended in public on

Monday 11 February 2019 at 12.45 hours

by

Weijie Du

born on 12 August 1988

in Neimongol, China

Supervisor:

Prof. dr. R.A. de Boer

Co-supervisor:

Dr. H.H.W. Sillje

Assessment Committee

Prof. dr. A.A. Voors

Prof. dr. P. Heeringa

Prof. dr. B. Schroen

Paranymphs:

Salva Yurista

Peijia Jiang

TABLE OF CONTENTS

Chapter 1

Introduction

9

Chapter 2

Novel heart failure biomarkers: why do we fail to

exploit their potential?

21

Chapter 3

MicroRNA-328, a Potential Anti-Fibrotic Target in

Cardiac Interstitial Fibrosis

55

Chapter 4

A novel oral available myeloperoxidase (MPO)

inhibitor delays cardiac remodeling in a pressure

overload mouse model

71

Chapter 5

Plasma levels of heart failure biomarkers are

primarily a reflection of extracardiac production

99

Chapter 6

Tissue plasma-biomarker expression in Ren2

hypertensive heart failure rats

139

Chapter 7

Summary, discussion and future perspectives

159

Samenvatting, discussie en toekomstperspectieven

169

Acknowledgements

177