Cover Page
The handle http://hdl.handle.net/1887/47467 holds various files of this Leiden University dissertation
Author: Welten, S.M.J.
Title: The role of 14q32 microRNAs in vascular remodelling
Issue Date: 2017-03-09
The role of 14q32 microRNAs in vascular remodelling
Sabine Welten
© S.M.J. Welten, 2017
ŽǀĞƌ͗/ŵŵƵŶŽŇƵŽƌĞƐĐĞŶƚƐƚĂŝŶŝŶŐŽĨĂŽƌƟĐƐƉƌŽƵƚƐŝŶŵƵƌŝŶĞĂŽƌƟĐƌŝŶŐĂƐƐĂLJ WƌŝŶƟŶŐ͗ZŝĚĚĞƌƉƌŝŶƚs͕dŚĞEĞƚŚĞƌůĂŶĚƐ
/^E͗ϵϳϴͲϵϰͲϲϮϵϵͲϱϮϲͲϬ
ůů ƌŝŐŚƚƐ ƌĞƐĞƌǀĞĚ͘ EŽ ƉĂƌƚ ŽĨ ƚŚŝƐ ƚŚĞƐŝƐ ŵĂLJ ďĞ ƌĞƉƌŽĚƵĐĞĚ͕ ĚŝƐƚƌŝďƵƚĞĚ Žƌ
ƚƌĂŶƐŵŝƩĞĚŝŶĂŶLJĨŽƌŵŽƌďLJĂŶLJŵĞĂŶƐ͕ǁŝƚŚŽƵƚƉƌŝŽƌǁƌŝƩĞŶƉĞƌŵŝƐƐŝŽŶŽĨƚŚĞ
ĂƵƚŚŽƌ͘
dŚĞƌŽůĞŽĨϭϰƋϯϮŵŝĐƌŽZEƐŝŶ
ǀĂƐĐƵůĂƌƌĞŵŽĚĞůůŝŶŐ
WƌŽĞĨƐĐŚƌŝŌ
ƚĞƌǀĞƌŬƌŝũŐŝŶŐǀĂŶ
ĚĞŐƌĂĂĚǀĂŶŽĐƚŽƌĂĂŶĚĞhŶŝǀĞƌƐŝƚĞŝƚ>ĞŝĚĞŶ͕
ŽƉŐĞnjĂŐǀĂŶZĞĐƚŽƌDĂŐŶŝĮĐƵƐƉƌŽĨ͘ŵƌ͘͘:͘:͘D͘^ƚŽůŬĞƌ͕
ǀŽůŐĞŶƐďĞƐůƵŝƚǀĂŶŚĞƚŽůůĞŐĞǀŽŽƌWƌŽŵŽƟĞƐ ƚĞǀĞƌĚĞĚŝŐĞŶŽƉϵŵĂĂƌƚϮϬϭϳ
ŬůŽŬŬĞϭϲ͘ϭϱƵƵƌ
ĚŽŽƌ
Sabine Marlies Janine Welten
'ĞďŽƌĞŶƚĞŵƐƚĞƌĚĂŵŝŶϭϵϴϴ
WƌŽŵŽƚŽƌ͗ WƌŽĨ͘Ěƌ͘W͘,͘͘YƵĂdž
ŽͲƉƌŽŵŽƚŽƌ͗ ƌ͘͘z͘EŽƐƐĞŶƚ
>ĞĚĞŶWƌŽŵŽƟĞĐŽŵŵŝƐƐŝĞ͗ WƌŽĨ͘Ěƌ͘,͘͘:͘ ŝŬĞŶŵ
WƌŽĨ͘Ěƌ͘:͘t͘:ƵŬĞŵĂ
WƌŽĨ͘Ěƌ͘D͘:͘d͘,͘'ŽƵŵĂŶƐ
WƌŽĨ͘Ěƌ͘͘:͘D͘ĚĞsƌŝĞƐ;D͕ŵƐƚĞƌĚĂŵͿ
ƌ͘Z͘͘ŽŽŶ;'ŽĞƚŚĞhŶŝǀĞƌƐŝƚćƚ͕&ƌĂŶŬĨƵƌƚĂŵDĂŝŶͿ
dŚĞƌĞƐĞĂƌĐŚĚĞƐĐƌŝďĞĚŝŶƚŚŝƐƚŚĞƐŝƐǁĂƐƐƵƉƉŽƌƚĞĚďLJƚŚĞEĞƚŚĞƌůĂŶĚƐ/ŶƐƟƚƵƚĞĨŽƌZĞŐĞŶĞƌĂƟǀĞ
DĞĚŝĐŝŶĞ ;E/ZD͕ & ^ϬϵϬϴͿ ĂŶĚ ǁĂƐ ƉĞƌĨŽƌŵĞĚ Ăƚ ƚŚĞ ĚĞƉĂƌƚŵĞŶƚ ŽĨ sĂƐĐƵůĂƌ ^ƵƌŐĞƌLJ͕ >ĞŝĚĞŶ
hŶŝǀĞƌƐŝƚLJDĞĚŝĐĂůĞŶƚĞƌ͕>ĞŝĚĞŶ͕dŚĞEĞƚŚĞƌůĂŶĚƐ͘
Table of contents
ŚĂƉƚĞƌϭ Part I
ŚĂƉƚĞƌϮ
ŚĂƉƚĞƌϯͲ/
ŚĂƉƚĞƌϯͲ//
ŚĂƉƚĞƌϰ
ŚĂƉƚĞƌϱ
Part II
ŚĂƉƚĞƌϲ
ŚĂƉƚĞƌϳ
Part III
ŚĂƉƚĞƌϴ
'ĞŶĞƌĂůŝŶƚƌŽĚƵĐƟŽŶĂŶĚŽƵƚůŝŶĞŽĨƚŚĞƐŝƐ 14q32 microRNAs in vascular remodelling
dŚĞŵƵůƟĨĂĐƚŽƌŝĂůŶĂƚƵƌĞŽĨŵŝĐƌŽZEƐŝŶǀĂƐĐƵůĂƌƌĞŵŽĚĞůůŝŶŐ
/ŶŚŝďŝƟŽŶŽĨϭϰƋϯϮŵŝĐƌŽZEƐŵŝZͲϯϮϵ͕ŵŝZͲϰϴϳď͕ŵŝZͲϰϵϰĂŶĚŵŝZͲϰϵϱ
ŝŶĐƌĞĂƐĞƐŶĞŽǀĂƐĐƵůĂƌŝnjĂƟŽŶĂŶĚďůŽŽĚŇŽǁƌĞĐŽǀĞƌLJĂŌĞƌŝƐĐŚĞŵŝĂ
>ĞƩĞƌƌĞŐĂƌĚŝŶŐĂƌƟĐůĞ͞DŝĐƌŽZEͲϭϱϱĞdžĞƌƚƐĐĞůůͲƐƉĞĐŝĮĐĂŶƟĂŶŐŝŽŐĞŶŝĐ
ďƵƚƉƌŽĂƌƚĞƌŝŽŐĞŶŝĐĞīĞĐƚƐĚƵƌŝŶŐĂĚĂƉƟǀĞŶĞŽǀĂƐĐƵůĂƌŝnjĂƟŽŶ͟
/ŶŚŝďŝƟŽŶŽĨŵŝĐƌŽZEͲϰϵϰƌĞĚƵĐĞƐĐĂƌŽƟĚĂƌƚĞƌLJĂƚŚĞƌŽƐĐůĞƌŽƟĐůĞƐŝŽŶ
ĚĞǀĞůŽƉŵĞŶƚĂŶĚŝŶĐƌĞĂƐĞƐƉůĂƋƵĞƐƚĂďŝůŝƚLJ
dŚĞƌŽůĞŽĨϭϰƋϯϮŵŝĐƌŽZEƐŝŶƌĞƐƚĞŶŽƐŝƐ͗ŝŶŚŝďŝƟŽŶŽĨƚŚĞϭϰƋϯϮ
ŵŝĐƌŽZEŵŝZͲϰϵϱƌĞĚƵĐĞƐůĞƐŝŽŶĨŽƌŵĂƟŽŶ͕ŝŶƟŵĂůŚLJƉĞƌƉůĂƐŝĂĂŶĚ ƉůĂƐŵĂĐŚŽůĞƐƚĞƌŽůůĞǀĞůƐŝŶĞdžƉĞƌŝŵĞŶƚĂůƌĞƐƚĞŶŽƐŝƐ
;ƉŽƐƚͿƚƌĂŶƐĐƌŝƉƟŽŶĂůƌĞŐƵůĂƟŽŶŽĨϭϰƋϯϮŵŝĐƌŽZEƐ
/ŶŚŝďŝƟŽŶŽĨDĞĨϮĂŝŶĐƌĞĂƐĞƐƉŽƐƚͲŝƐĐŚĞŵŝĐŶĞŽǀĂƐĐƵůĂƌŝnjĂƟŽŶǀŝĂϭϰƋϯϮ
ŵŝĐƌŽZEƐŵŝZͲϯϮϵĂŶĚŵŝZͲϰϵϰ
WŽƐƩƌĂŶƐĐƌŝƉƟŽŶĂůƌĞŐƵůĂƟŽŶŽĨϭϰƋϯϮŵŝĐƌŽZEŵŝZͲϯϮϵĚƵƌŝŶŐ
ǀĂƐĐƵůĂƌƌĞŐĞŶĞƌĂƟŽŶĂŌĞƌŝƐĐŚĞŵŝĂ ϭϰƋϯϮŵŝĐƌŽZEƐŝŶĂĚŝƉŽƐĞƟƐƐƵĞ
hƉƌĞŐƵůĂƟŽŶŽĨϭϰƋϯϮŵŝĐƌŽZEƐŝŶŚƵŵĂŶƐƵďĐƵƚĂŶĞŽƵƐĂĚŝƉŽƐĞ
ƟƐƐƵĞƐĂŵƉůĞƐŽĨƉĂƟĞŶƚƐǁŝƚŚĐƌŝƟĐĂůůŝŵďŝƐĐŚĞŵŝĂƵŶĚĞƌŐŽŝŶŐŵĂũŽƌ
ĂŵƉƵƚĂƟŽŶ
ϵ
27
ϱϵ
107
ϭϭϯ
ϭϯϳ
ϭϲϯ
ϭϴϭ
201
Part IV
ŚĂƉƚĞƌϵ ^ƵŵŵĂƌLJĂŶĚĨƵƚƵƌĞƉĞƌƐƉĞĐƟǀĞƐ EĞĚĞƌůĂŶĚƐĞ^ĂŵĞŶǀĂƫŶŐ
>ŝƐƚŽĨWƵďůŝĐĂƟŽŶƐ
ƵƌƌŝĐƵůƵŵsŝƚĂĞ
Ϯϭϵ Ϯϯϭ Ϯϯϵ Ϯϰϱ
