Atherosclerotic plaques develop preferentially in curved and branching arteries in-vivo.
Lipids and inflammatory cells accumulation in the intimal layer of the arterial wall
is considered as the main driving mechanism in the disease progression. Evidences
suggest that this focal distribution of plaques may result from the combination of
systemic risk factors including high plasma cholesterol, smoking, diabetis, hypertension
or genetic pre-disposition and local hemodynamic risk factors such as low and
oscillatory flows. The exact mechanism of the biological and biomechanical
interactions between the endothelium, blood flow and the growing lesion underneath
still remains unclear.
This thesis is a study on the relationship between biomechanical factors found in proatherogenic
flow and endothelial inflammation. The thesis focuses in particular on the
effect of secondary flows on wall shear stress and mass transport distribution. To that
end, we have combined different techniques from flow imaging, 3D flow
reconstruction, vascular biology and mathematical simulation of biological network.
In particular, shear stress is involved in the regulation of the pro-inflammatory
transcription factor nuclear factor -kB (NF-kB) and the vasoregulator Nitric Oxide. The
role of endothelial Nitric Oxide and wall shear stress on NF-kB activation is still
controversial. We investigated here the hypothesis that NO negatively regulates NF-
kB activation in flow chamber with sheared endothelial cells and using a mathematical
model of the NF-kB-NO pathway.
Understanding the underlying relationship between hemodynamic factors and
inflammatory cells transport to the wall may contribute to the development of better
therapies or interventional practices to treat patients with atherosclerotic diseases
