The pathophysiology of atherosclerosis is complex and multifactorial, involving systemic risk factors and biomechanical stimuli. Atherosclerotic plaques predominantly form in regions that are exposed to low shear stress of the blood at the vessel wall, whereas regions of moderate and high shear stress are generally protected. For more than 20 years, my research group performs studies to investigate the role of shear stress in atherosclerotic plaque formation and rupture in coronary and carotid

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... rteries of patients and laboratory animals. For that reason, new technology was developed to 3D reconstruct arteries based on fusion of multiple invasive and noninvasive imaging modalities. These 3D reconstructions were used as input for computational fluid mechanics to derive the local shear stress. We noticed that if the lumen was not affected by the disease, because of outward remodeling, plaques were mainly located at low shear stress regions. However, at later stages of the disease if lumen narrowing occurred, the plaque is also exposed to high shear stress. Until now it is not fully clear, what the influence is of high shear stress on these advanced lumen intruding plaques. Evidence is accumulating for a role of high shear stress in changes in plaque composition towards plaque destabilization and eventually plaque rupture. Moreover, not much studies investigated the influence of multidirectional shear stress on plaque progression and destabilization. In this lecture I will present the research that my group performed to investigate the role of (multidirectional) shear stress on plaque progression, destabilization and rupture at different stages of the atherosclerotic disease.