Exploring vascular aging in ERCC1-deficient mice and progressing toward human vessel-on-a-chip models

Janette van der Linden

Exploring vascular aging in ERCC1-deficient mice and progressing toward human vessel-on-a-chip models

Janette van der Linden

Molecular Genetics

Research output: Types of Thesis › Doctoral Thesis › Internal

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Abstract

Cardiovascular diseases are the number one cause of death globally. The most important
determinant of cardiovascular health is a person’s age. Aging results in structural changes
and functional decline of the cardiovascular system. DNA damage is an important
contributor to the aging process, and mice with a DNA repair defect caused by Ercc1
deficiency display hypertension, vascular stiffening, and loss of vasomotor control.

In this thesis we investigated RAS alterations by assessing intrarenal renin activity in
Ercc1Δ/− mice using the renin-activated, near-infrared fluorescent probe ReninSense680™.
Furthermore, we aimed to characterize vascular aging in mice with hampered ERCC1
function. Building on these insights, we further examined the calcification potential of
VSMCs with an ERCC1 mutation and investigated the molecular mechanisms underlying
the effects of dietary restriction (DR), a well-known anti-aging intervention, on vascular
aging.

Original language	English
Awarding Institution	Erasmus University Rotterdam
Supervisors/Advisors	Danser, Jan, Supervisor van der Pluijm, Ingrid, Co-supervisor Roks, Anton J.M., Co-supervisor Cheng, Caroline, Co-supervisor
Award date	21 Jan 2026
Place of Publication	Rotterdam
Publisher	Erasmus University Rotterdam (EUR)
Publication status	Published - 21 Jan 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

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title = "Exploring vascular aging in ERCC1-deficient mice and progressing toward human vessel-on-a-chip models",

abstract = "Cardiovascular diseases are the number one cause of death globally. The most important determinant of cardiovascular health is a person{\textquoteright}s age. Aging results in structural changes and functional decline of the cardiovascular system. DNA damage is an important contributor to the aging process, and mice with a DNA repair defect caused by Ercc1 deficiency display hypertension, vascular stiffening, and loss of vasomotor control. In this thesis we investigated RAS alterations by assessing intrarenal renin activity in Ercc1Δ/− mice using the renin-activated, near-infrared fluorescent probe ReninSense680{\texttrademark}. Furthermore, we aimed to characterize vascular aging in mice with hampered ERCC1 function. Building on these insights, we further examined the calcification potential of VSMCs with an ERCC1 mutation and investigated the molecular mechanisms underlying the effects of dietary restriction (DR), a well-known anti-aging intervention, on vascular aging. ",

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T1 - Exploring vascular aging in ERCC1-deficient mice and progressing toward human vessel-on-a-chip models

AU - van der Linden, Janette

PY - 2026/1/21

Y1 - 2026/1/21

N2 - Cardiovascular diseases are the number one cause of death globally. The most important determinant of cardiovascular health is a person’s age. Aging results in structural changes and functional decline of the cardiovascular system. DNA damage is an important contributor to the aging process, and mice with a DNA repair defect caused by Ercc1 deficiency display hypertension, vascular stiffening, and loss of vasomotor control. In this thesis we investigated RAS alterations by assessing intrarenal renin activity in Ercc1Δ/− mice using the renin-activated, near-infrared fluorescent probe ReninSense680™. Furthermore, we aimed to characterize vascular aging in mice with hampered ERCC1 function. Building on these insights, we further examined the calcification potential of VSMCs with an ERCC1 mutation and investigated the molecular mechanisms underlying the effects of dietary restriction (DR), a well-known anti-aging intervention, on vascular aging.

AB - Cardiovascular diseases are the number one cause of death globally. The most important determinant of cardiovascular health is a person’s age. Aging results in structural changes and functional decline of the cardiovascular system. DNA damage is an important contributor to the aging process, and mice with a DNA repair defect caused by Ercc1 deficiency display hypertension, vascular stiffening, and loss of vasomotor control. In this thesis we investigated RAS alterations by assessing intrarenal renin activity in Ercc1Δ/− mice using the renin-activated, near-infrared fluorescent probe ReninSense680™. Furthermore, we aimed to characterize vascular aging in mice with hampered ERCC1 function. Building on these insights, we further examined the calcification potential of VSMCs with an ERCC1 mutation and investigated the molecular mechanisms underlying the effects of dietary restriction (DR), a well-known anti-aging intervention, on vascular aging.

M3 - Doctoral Thesis

PB - Erasmus University Rotterdam (EUR)

CY - Rotterdam

ER -

Exploring vascular aging in ERCC1-deficient mice and progressing toward human vessel-on-a-chip models

Abstract

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