7-Ketocholesterol in disease and aging

Abstract

7-Ketocholesterol (7KC) is a toxic oxysterol that is associated with many diseases and disabilities of aging, as well as several orphan diseases. 7KC is the most common product of a reaction between cholesterol and oxygen radicals and is the most concentrated oxysterol found in the blood and arterial plaques of coronary artery disease patients as well as various other disease tissues and cell types. Unlike cholesterol, 7KC consistently shows cytotoxicity to cells and its physiological function in humans or other complex organisms is unknown. Oxysterols, particularly 7KC, have also been shown to diffuse through membranes where they affect receptor and enzymatic function. Here, we will explore the known and proposed mechanisms of pathologies that are associated with 7KC, as well speculate about the future of 7KC as a diagnostic and therapeutic target in medicine.

Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases

“…The oxidative stress as well as the mitochondrial and peroxisomal dysfunction associated with 7KC-induced oxiapoptophagy are strongly reduced. Since 7KC is associated with cardiovascular diseases, eye diseases (cataract, AMD) and bowel diseases [ 28 , 30 , 31 , 59 ], our data support that these polyphenols widely represented in the Mediterranean diet, which can be incorporated in food supplements, could be of interest to prevent and/or treat these age-related and chronic inflammatory diseases. However, from a pharmacological point of view, due to the limited bioavailability of polyphenols in vivo, chemical and galenic strategies should be considered and must be developed to preserve their efficacy.…”

“…In the present study, the cytotoxicity of 7KC was characterized in neuronal N2a cells and the ability of polyphenols, abundant in the Mediterranean diet (RSV, QCT and API), to counteract the harmful effects of this oxysterol was determined. Preventing the cytotoxicity of 7KC with polyphenols could be a means of treating certain neurodegenerative diseases associated with oxidative stress resulting from increased levels of 7KC, such as AD [ 32 ] as well as other age-related diseases [ 28 , 31 ]. The results obtained with the three polyphenols (RSV, QCT and API) show that these molecules are oppose 7KC-induced oxiaoptophagy.…”

“…leading to the Fenton and Haber–Weiss reactions) [ 27 ]. Although the biogenesis pathway of 7KC by auto-oxidation is considered to be preponderant [ 28 ], 7KC can also be formed enzymatically by the enzyme 11β-HSD2 from 7β-hydroxycholesterol in some cells and from 7-dehydrocholesterol by the enzyme CYP7A1 [ 29 ]. Therefore, to oppose the detrimental effects of 7KC (oxidative stress, inflammation and cell death), it is judicious to find molecules opposing these cytotoxic effects, or strategies that contribute to its biodegradation [ 29 , 30 ], rather than by using enzyme inhibitors.…”

A lipid atlas of human carotid atherosclerosis

“…7-Ketocholesterol has been found in atherosclerotic tissue before 26,27,32 and shown to play a pro-atherogenic role, e.g. by mediating cell death 33,34 .…”

The Lord of the NanoRings: Cyclodextrins and the battle against SARS-CoV-2

“…Cholesterol, which is known to participate in the integrity and fluidity of bilayers, is one of the main components of these lipids rafts (Krause and Regen, 2014). Several diseases, such as Alzheimer, cancer, and atherosclerosis, have been related to the presence of cholesterol and other sterol derivatives in biological membranes (Anderson et al, 2020;Taylor and Hooper, 2007). The fluidity of membranes is a key point in the interaction between viruses and cells (Yang et al, 2016).…”