Discovering the Dynamics of Endothelial Shear Stress

The interaction between blood flow and the endothelium has been proposed to
play a role in the atherosclerotic disease process. Low ESS promotes increased
permeability and enhanced low-density lipoprotein cholesterol uptake into the
artery wall.These processes are known to facilitate arterial remodeling.
Furthermore, ESS regulates endothelium-derived NO, which plays a central role
in the regulation of large-artery stiffness in vivo. Despite these data from in
vitro and animal studies, the relationship between ESS and arterial remodeling
and arterial stiffness has not been investigated in vivo in humans. The
scarcity of data on this topic is predominantly because accurate quantification
methods to estimate ESS in vivo are challenging to create. Most existing
approaches either use highly complicated methods such as computed fluid
dynamics, which are unmanageable in trials investigating larger populations, or
use oversimplified methods that assume Poiseuille flow.Similarly, assessment of
arterial stiffness as well as arterial structure is technically difficult. We
therefore developed a noninvasive 3.0-T MRI protocol that enables
quantification of all these dimensional and functional aspects in a single MRI
scanning session. We based our ESS assessment on velocity gradient modelling
comparable to methods previously used by Oyre et al.We determined excellent
reproducibility and a role for endothelial stress in arterial remodelling and
arterial stiffness in humans. Here, we propose to further elucidate
determinants of endothelial shear stress and to establish the relation between
endothelial function and endothelial shear stress in humans.

2.1 Primary Objective
To determine the effect of endothelial dependent and independent vasodilators
on endothelial shear stress in humans.


2.2 Secondary Objective
To determine the association between endothelial shear stress and endothelial
function in humans.


2.3. Tertiary Objective
To determine the effect of endothelial dependent and independent vasodilators
on wall shear stress during a low grade inflammatory response.

This is a cross-sectional study.

Patients receive no direct benefits. They have to visit the AMC 1-2 times for a
four hour visit.
Maximal invasive procedures are the blood withdrawahl and the vaccination (for
healthy controls only).
Patients can perceive the FMD as strenuous due to the tight cuff around the
upper arm.
Patients will get two different vaso-active medications with a short half-life.
Patient will get a MRI examination.
The associated risk for all procedures is minimal.