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The removal of the toxic oxidized cholesterol, 7-ketocholesterol (7KC), from cells through the administration of therapeutics has the potential to treat atherosclerosis and various other pathologies. While cholesterol is a necessary building block for homeostasis, oxidation of cholesterol can lead to the formation of toxic oxysterols with 7KC being the most prominent. 7KC is primarily formed through the non-enzymatic oxidation of cholesterol and is found in high levels in oxidized LDL (oxLDL) particles, which are highly implicated in heart disease. 7KC is implicated in the pathogenesis of numerous diseases, including multiple sclerosis, hypercholesterolemia, sickle cell anemia, and multiple age-related diseases. Of particular interest is the role of 7KC in the progression of atherosclerosis, with several studies associating elevated 7KC levels with the etiology and severity of the disease and in the underlying transition of macrophages to foam cells.
Bhargava P, Dinh D, Teramayi F, Silberg A, Petler N, Anderson AM, Sadrerafi K, Clemens DM, O’Connor MS. Selective removal of 7-ketocholesterol by a novel atherosclerosis therapeutic candidate reverts foam cells to a macrophage-like phenotype. Atherosclerosis. 2025; 409:119217. https://doi.org/10.1016/j.atherosclerosis.2025.119217.