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Objectives An endothelium dysfunction is thought to play a crucial role in the atherosclerosis development and progression, but its structural basis is not fully understood. Therefore the purpose of this study is to determine patterns of endothelium ultrastructural changes in relation to a plaque structure. Methods 34 specimens, taken from 7 atherosclerotic plaques in the internal carotid artery, were analyzed using light and transmission electron microscopy; plaque structure, subendothelial layer composition and ultrastructural characteristics of endotheliocytes were quantitatively assessed and then used for correlation analysis. Results Observations included: (i) regions of the endothelial denudation; (ii) intercellular gaps; (iii) simplification and loss of cell-cell junctions; (iv) ultrastructural changes such as marked variety of the endotheliocytes size and profile, various degrees of cytoplasm edema or dehydration, distribution of cytoskeletal fibers as well as different number and functional status of organelles. Data suggested a correlation between the aggravation of some processes contributing to the plaque unstable structure (namely edema and decomposition of the extracellular matrix, volume of the atheromatosis in the plaque) and a number of ultrastructural changes of the endothelium (size of denudated areas, signs of the alteration in barrier function and protein synthesis, dystrophic and necrobiotic changes of endotheliocytes, weakening of their connections to the subendothelial layer). Degree of aforementioned changes of the endothelium decreased with an increase of collagenous and elastic fibers quantity in the subendothelial layer. Conclusions Preserved endothelial cells of the advanced atherosclerotic plaque displayed pronounced ultrastructural pathology, which differed significantly depending on plaque and subendothelial layer structure.