Download Impaired cardiac thyroid hormone signaling during heart failure

Impaired cardiac thyroid hormone signaling during heart failure
The role of type III deiodinase
ISBN: 978-94-6203-042-8
Cover design: Fishtankmedia.nl
Printed by: Wöhrmann Print service
Financial support for printing of this thesis was kindly provided by Stichting Dondersfonds.
The research presented in this thesis was performed at the Department of Physiology,
Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The
Netherlands.
© 2012 C.J. Pol
VRIJE UNIVERSITEIT
Impaired cardiac thyroid hormone signaling during heart failure
The role of type III deiodinase
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad Doctor aan
de Vrije Universiteit Amsterdam,
op gezag van de rector magnificus
prof.dr. L.M. Bouter,
in het openbaar te verdedigen
ten overstaan van de promotiecommissie
van de Faculteit der Geneeskunde
op donderdag 27 september 2012 om 15.45 uur
in de aula van de universiteit,
De Boelelaan 1105
door
Christiana Jantina Pol
geboren te Woerden
promotor:
prof.dr. W.J. Paulus
copromotor:
dr. W.S. Simonides
The research described in this thesis was supported by a grant of the Netherlands Heart
Foundation (NHF-2006B240).
Financial support by the Netherlands Heart Foundation for the publication of this thesis is
gratefully acknowledged.
I almost wish I hadn’t
gone down that rabbit-hole
- and yet - and yet it’s rather curious, you know,
this sort of life!
Alice in Wonderland, 1865
Overige leden promotiecommissie:
prof.dr. A.J.G. Horrevoets
prof.dr. H.W.M. Niessen
prof.dr. A.C. van Rossum
prof.dr. D. Salvatore
prof.dr. Ir. T.J. Visser
Contents
Abbreviations
8
Chapter 1
Introduction
11
Chapter 2
In vivo measurement of T3-dependent transcription activity
35
Chapter 3
Left-ventricular remodeling following myocardial infarction is associated
with a cardiomyocyte-specific hypothyroid condition
Chapter 4
Effects of exercise training on LV function and post-MI remodeling: role of
type III deiodinase?
Chapter 5
77
Type III deiodinase expression during early post-MI remodeling and its
regulation
Chapter 6
51
91
Early post-MI induction of type III deiodinase expression is associated with
increased HIF-1 signaling
113
Chapter 7
Cardiac induction of type III deiodinase in human ischemic heart disease
129
Chapter 8
Summary and general discussion
143
Samenvatting – Summary in Dutch
167
Dankwoord – Acknowledgements
173
Author affiliations
176
List of publications
177
Curriculum Vitae
178
Abbreviations
ANF/ANP
atrial natriuretic factor
BNP
brain natriuretic peptide
CHF
congestive heart failure
CSA
cross-sectional area
CVD
cardiovascular diseases
DFO
deferoxamine
DIO1
type I deiodinase
DIO2
type II deiodinase
DIO3
type III deiodinase
EDD
end-diastolic diameter
EDP
end-diastolic pressure
ERK
extracellular signal-regulated kinase
ESD
end-systolic diameter
ESP
end-systolic pressure
FLuc
Firefly luciferase
FS
fractional shortening
HIF-1Į
hypoxia-inducible factor-1Į
HPRT
hypoxanthine-guanine phosporibosyltransferase
HRE
HIF binding sites
ISHD
ischemic heart disease
JAK/STAT
Janus kinase/signal transducer and activator of transcription
JNK
c-Jun N-terminal kinases
LCA
left coronary artery
LV dP/dtmax
maximum rate of rise of LV pressure
LV dP/dtmin
maximum rates of fall of LV pressure
LV dP/dtp30
rate of rise of LV pressure at 30 mmHg
LV
left ventricle
MAPK
mitogen-activated protein kinase
MHC
myosin heavy chain
MI
myocardial infarction
mTOR
mammalian target of rapamycin
NTIS
non-thyroidal illness sydrome
PAH
pulmonary arterial hypertension
PI3K
phosphoinositide 3-kinase
PLB
phospholamban
Ptch1
patched-1 receptor
RAAS
renin-angiotensin-aldosterone system
RLuc
Renilla luciferase
rT3
3,3’,5’-triiodothyronine
RV
right ventricle
SERCA
sarco/endoplasmic reticulum Ca2+-ATPase
Shh
Sonic hedgehog
T2
3,3’-diiodothyronine
T3
3,5,3’-triiodothyronine
T4
3,5,3’,5’-tetraiodothyronine
TGFȕ
transforming growth factor ȕ
TH
thyroid hormone
TMAs
tissue microarrays
TR
thyroid hormone receptor
TRE
thyroid hormone response element
TSH
thyroid-stimulating-hormone
VEGF
vascular endothelial growth factor
IJ
time constant of ventricular relaxation