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The vascular endothelium, a monolayer of endothelial cells (ECs), is an important regulatory \"organ\" critical for cardiovascular homeostasis in health which also contributes significantly to the pathomechanisms of several disease states, including atherosclerosis. Over the years, there has been evidence highlighting the central role of endoplasmic reticulum (ER) in the maintenance of endothelial function and perturbations in ER biology have been proposed to adversely affect a diverse range of endothelial functions. Of particular interest is the evidence that under certain pathophysiological circumstances, abnormal ER ultrastructure correlates with altered ER function and signaling and can contribute to cell injury and apoptosis. Therefore, the ultrastructural traits of ER membranes can have important implications not only for their functional bearings but also for the etiology and pathophysiology of diverse human disorders. With regard to atherosclerosis, the focus of ER research\u00a0has\u00a0been centered on the molecular signals originated from the ER to manage conditions of stress, leaving the fine structure of this organelle an almost unexplored (but promising) area of studies. There is, also, increasing evidence that mitochondrial dysfunction plays a critical role in promoting cell apoptosis, inflammation, and oxidative stress, thereby contributing to atheroma growth. It is within this context that the present study has been undertaken to investigate the microscopic architecture of ECs in human atherosclerosis and to determine whether the potential structural abnormalities of ER and mitochondria may play a central pathogenic role in atherogenesis or may merely reflect the condition of a tissue whose integrity has already been disturbed or destroyed. For this purpose, transmission electron microscopy (TEM) remains a powerful technique that can not only provide information about the ultrastructural state of cell organelles but also allow the correlation between different subcellular alterations indicative of a certain pathophysiological condition and cellular response. The present study expands the spectrum of ultrastructural defects known to exist in human atherosclerosis and suggests that ER alterations may be of great importance in the pathogenesis of the disease. The architectural changes of ER may be considered early pathological events that precede any overt histologic abnormalities in the vascular endothelium and its subcellular organelles, primarily the mitochondrial pool.<\/jats:p>","DOI":"10.1111\/joa.13281","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T20:20:48Z","timestamp":1596226848000},"page":"1015-1025","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The microscopic anatomy of endothelial cells in human atherosclerosis: Focus on ER and mitochondria"],"prefix":"10.1111","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9061-9776","authenticated-orcid":false,"given":"Ida","family":"Perrotta","sequence":"first","affiliation":[{"name":"Centre for Microscopy and Microanalysis, Transmission Electron Microscopy Laboratory Department of Biology, Ecology and Earth Sciences (Di.B.E.S.T.) 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