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The development and subsequent rupture of atherosclerotic plaques in human carotid arteries is a major cause of ischaemic stroke. Mechanical characterization of atherosclerotic plaques can aid our understanding of this rupture risk. Despite this however, experimental studies on human atherosclerotic carotid plaques, and fibrous plaque caps in particular, are very limited. This study aims to provide further insights into atherosclerotic plaque rupture by mechanically testing human fibrous plaque caps, the region of the atherosclerotic lesion most often attributed the highest risk of rupture. The results obtained highlight the variability in the ultimate tensile stress, strain and stiffness experienced in atherosclerotic plaque caps. By pre-screening all samples using small angle light scattering (SALS) to determine the dominant fibre direction in the tissue, along with supporting histological analysis, this work suggests that the collagen fibre alignment in the circumferential direction plays the most dominant role for determining plaque structural stability. The work presented in this study could provide the basis for new diagnostic approaches to be developed, which non-invasively identify carotid plaques at greatest risk of rupture. Mechanical characterisation of the atherosclerotic plaque cap is of utmost importance for understanding the mechanisms that govern the rupture strength of this tissue in-vivo. Studies has shown that plaque tissue is heterogenous and comprises of many structural components, each of which exhibits a varying mechanical response. However, rupture generally is located to the plaque cap, whereby the stress exerted on this location exceeds its mechanical strength causing failure. This work shows, for the first time, that the underlying collagen fibre architecture of carotid plaque caps governs their strength and stiffness. This study shows that plaque caps with collagen fibres aligned in the predominately circumferential direction experience higher stresses and lower strains before failure while those with predominately axial fibres display the opposite trend. Furthermore, total collagen content was found not to play a dominant role in determining the mechanical response of the tissue. The present study provides critical insights into human atherosclerotic plaque tissue mechanics and offers clinically relevant insights for mechanically sensitive imaging techniques, such as strain-based ultrasound or MRI. [Display omitted] [ABSTRACT FROM AUTHOR]