Wall shear stress and local plaque development in stenosed carotid arteries of hypercholesterolemic minipigs

Abstract

BACKGROUND: Wall shear stress is thought to play a critical role in the local development of atherosclerotic plaque and to affect plaque vulnerability. However, current models and hypotheses do not fully explain the link between wall shear stress and local plaque development. We aimed to investigate the relation between wall shear stress and local plaque development in surgically induced common carotid artery stenoses of hypercholesterolemic minipigs. MATERIALS, METHODS AND RESULTS: We created a surgically induced stenosis of the common carotid artery in 10 minipigs using a perivascular collar. We documented the flow and shear stress changes by ultrasound, magnetic resonance imaging, and computational fluid dynamics. Carotid plaques were documented by microscopy. Atherosclerotic lesions, in both pre-stenotic and post-stenotic segments, were associated with thrombus in the stenosed segment. In patent carotid arteries, atherosclerotic lesions were found in the post-stenotic segments only. Atherosclerotic lesions developed where low and oscillatory shear stress were present simultaneously, whereas low or oscillatory shear stress alone did not lead to lesion formation. CONCLUSIONS: Low and oscillatory shear stress in combination promoted plaque development, including plaques with necrotic cores that are the key and dangerous characteristic of vulnerable plaques.