7-Ketocholesterol in disease and aging

Amelia Anderson, Angielyn Campo, Elena Fulton, Anne Corwin, W Gray Jerome 3rd, Matthew S O'Connor, Amelia Anderson, Angielyn Campo, Elena Fulton, Anne Corwin, W Gray Jerome 3rd, Matthew S O'Connor

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.

Conflict of interest statement

The authors would like to disclose that Matthew O'Connor and Amelia Anderson have a founding interest in Underdog Pharmaceuticals LLC. This company is developing drugs that target toxic cholesterols such as 7-ketocholesterol.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
7KC can be nonenzymatically produced via oxidation of cholesterol along multiple different pathways.
Fig. 2
Fig. 2
Formation of foam cells and arterial plaque due to 7KC-induced differentiation and buildup of ROS.
Fig. 3
Fig. 3
7KC promotes vascular calcification via Pi-mediated apoptosis and disruption of autophagy-lysosomal pathway (ALP) in smooth muscle cells (SMCs).

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