Cholesterol-induced toxicity: An integrated view of the role of cholesterol in multiple diseases

Cell Metab. 2021 Oct 5;33(10):1911-1925. doi: 10.1016/j.cmet.2021.09.001. Epub 2021 Sep 24.

Abstract

High levels of cholesterol are generally considered to be associated with atherosclerosis. In the past two decades, however, a number of studies have shown that excess cholesterol accumulation in various tissues and organs plays a critical role in the pathogenesis of multiple diseases. Here, we summarize the effects of excess cholesterol on disease pathogenesis, including liver diseases, diabetes, chronic kidney disease, Alzheimer's disease, osteoporosis, osteoarthritis, pituitary-thyroid axis dysfunction, immune disorders, and COVID-19, while proposing that excess cholesterol-induced toxicity is ubiquitous. We believe this concept will help broaden the appreciation of the toxic effect of excess cholesterol, and thus potentially expand the therapeutic use of cholesterol-lowering medications.

Keywords: cell dysfunctions; cholesterol; cholesterol accumulation; cholesterol homeostasis; cholesterol toxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / therapeutic use
  • Atherosclerosis / diagnosis
  • Atherosclerosis / drug therapy
  • Atherosclerosis / epidemiology
  • Atherosclerosis / metabolism*
  • Biomarkers / metabolism
  • COVID-19 / diagnosis
  • COVID-19 / epidemiology
  • COVID-19 / metabolism*
  • COVID-19 Drug Treatment
  • Cholesterol / metabolism*
  • Humans
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / epidemiology
  • Hypercholesterolemia / metabolism*
  • Prognosis
  • Risk Factors

Substances

  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol