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Title: Hemodynamics and endothelial cell biology in cardiovascular diseases
Author: Foin, Nicolas
ISNI:       0000 0004 2700 0705
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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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.
Supervisor: Krams, Robert ; Caro, Colin Sponsor: Japanese Society for the Promotion of Science
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral