An insight on 7- ketocholesterol mediated inflammation in atherosclerosis and potential therapeutics

Steroids. 2021 Aug:172:108854. doi: 10.1016/j.steroids.2021.108854. Epub 2021 Apr 27.

Abstract

7-ketocholesterol, a toxic oxidative product of oxysterol is a causative agent of several diseases and disabilities concomitant to aging including cardiovascular diseases like atherosclerosis. Auto-oxidation of cholesterol esters present in low-density lipoprotein (LDL) deposits lead to the formation of oxidized LDL (Ox-LDL) along with its byproducts, namely 7KCh. It is predominantly found in atherosclerotic plaque and also found to be more atherogenic than cholesterol by being cytotoxic, interfering with cellular homeostasis. This makes it a serious threat by being the foremost cause of morbidity and mortality worldwide and is likely to become more serious during forth coming years. It involves in mediating inflammatory mechanisms characterized by the advancement of fibroatheroma plaques. The atherosclerotic lesion is composed of Ox-LDL along with fibrotic mass consisting of immune cells and molecules. Macrophages being the specialized phagocytic cells, contribute to removal of detrimental contents of the lesion along with accumulated lipids leading to alteration of its biology and functionality due to its plasticity. Here, we have explored the known as well as proposed mechanisms involved with 7KCh associated atherogenesis along with potential therapeutic strategies for targeting 7KCh as a diagnostic and target in medicine.

Keywords: 7-Ketocholesterol; Atherosclerosis; Low-density lipoprotein (LDL); Macrophages; Oxidized LDL (Ox-LDL).

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology*
  • Enzyme Inhibitors / adverse effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / pathology*
  • Ketocholesterols / adverse effects*

Substances

  • Enzyme Inhibitors
  • Ketocholesterols
  • 7-ketocholesterol