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Cellular effects of EZE, EZE\u2010Glu, and the low\u2010absorbable EZE\u2010analogue S6130 were investigated on human monocyte\u2010derived macrophages upon loading with atherogenic lipoproteins. EZE and S6130, but not EZE\u2010Glu disturbed the colocalization of CD13 and its coreceptor CD64 (Fc\u03b3 receptor I) in membrane microdomains, and decreased the presence of both receptors in detergent\u2010resistant membrane fractions. Biotinylated cholesterol absorption inhibitor C\u20105 (i.e., derivative of EZE) was rapidly internalized to perinuclear tubular structures of cells, resembling endoplasmic reticulum (ER), but CD13 was detected on extracellular sites of the plasma membrane and endolysosomal vesicles. Administration of EZE, but not of EZE\u2010Glu or S6130, was associated with decreased cellular cholesteryl ester content, indicating the sterol\u2010O acyltransferase 1 (SOAT1)\u2010inhibition by EZE. Furthermore, EZE decreased the expression of molecules involved in cholesterol uptake and synthesis, in parallel with increased apolipoprotein A\u2013I\u2010mediated cholesterol efflux and upregulation of efflux\u2010effectors. However, NPC1L1 the other claimed molecular target of EZE, was not detected in macrophages, thereby excluding this protein as target for EZE in macrophages. Thus, EZE is very likely a CD13\u2010linked microdomain\u2010disruptor and SOAT1\u2010inhibitor in macrophages leading to <jats:italic>in vitro<\/jats:italic> anti\u2010atherosclerotic effects through a decrease of net cellular cholesterol content. \u00a9 2019 International Society for Advancement of Cytometry<\/jats:p>","DOI":"10.1002\/cyto.a.23772","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T18:50:39Z","timestamp":1555527039000},"page":"869-884","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nonglucuronidated Ezetimibe Disrupts CD13\u2010 and CD64\u2010Coassembly in Membrane Microdomains and Decreases Cellular Cholesterol Content in Human Monocytes\/Macrophages"],"prefix":"10.1002","volume":"95","author":[{"given":"Evelyn","family":"Ors\u00f3","sequence":"first","affiliation":[{"name":"Institute for Clinical Chemistry and Laboratory Medicine University Hospital of 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