7-keto Cholesterol-d7 is intended for use as an internal standard for the quantification of 7-keto cholesterol by GC- or LC-MS. 7-keto Cholesterol is a bioactive sterol and a major oxysterol component of oxidized LDL.[1],[2] It is produced by oxidation of cholesterol via ethanol-mediated lipid peroxidation or photodamage as well as oxidation of 7-dehydro cholesterol by the cytochrome P450 (CYP) isoform CYP7A1.[3],[4],[5] 7-keto Cholesterol inhibits CYP7A1 (IC50 = ~1 μM).4 It induces activation and chemotaxis of retinal microglia as well as polarization to a pro-inflammatory state via NLRP3 inflammasome activation in vitro.[6] Intraocular implantation of 7-keto cholesterol-coated wafers increases ocular levels of VEGF, IL-1β, and GRO/KC, macrophage infiltration, and neovascularization in rat eye.[7] Levels of 7-keto cholesterol in lipid deposits are increased in a variety of chronic diseases, including atherosclerosis, Alzheimer's disease, and age-related macular degeneration.
Reference:
[1]. Shentu, T.P., Titushkin, I., Singh, D.K., et al. oxLDL-induced decrease in lipid order of membrane domains is inversely correlated with endothelial stiffness and network formation. American Journal of Physiology.Cell Physiology 299(2), C218-C229 (2010).
[2]. Brown, A.J., Leong, S.l., Dean, R.T., et al. 7-Hydroperoxycholesterol and its products in oxidized low density lipoprotein and human atherosclerotic plaque. Journal of Lipid Research 38, 1730-1745 (1997).
[3]. Rodriguez, I.R., and Fliesler, S.J. Photodamage generates 7-keto- and 7-hydroxycholesterol in the rat retina via a free radical-mediated mechanism. Photochemistry and Photobiology 85(5), 1116-1125 (2009).
[4]. Shinkyo, R., Xu, L., Tallman, K.A., et al. Conversion of 7-dehydrocholesterol to 7-ketocholesterol is catalyzed by human cytochrome P450 7A1 and occurs by direct oxidation without an epoxide intermediate. The Journal of Biological Chemisty 286(38), 33021-33028 (2011).
[5]. Mitic, T., Shave, S., Semjonous, N., et al. 11β-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo. Biochemical Pharmacology 86(1), 146-153 (2013).
[6]. Indaram, M., Ma, W., Zhao, L., et al. 7-Ketocholesterol increases retinal microglial migration, activation, and angiogenicity: A potential pathogenic mechanism underlying age-related macular degeneration. Sci. Rep. 5:9144, (2015).
[7]. Amaral, J., Lee, J.W., Chou, J., et al. 7-Ketocholesterol induces inflammation and angiogenesis in vivo: A novel rat model. PLoS One 8(2), e56099 (2013).