Mouse models of atherosclerosis in translational research

Trends Pharmacol Sci. 2022 Nov;43(11):920-939. doi: 10.1016/j.tips.2022.06.009. Epub 2022 Jul 25.

Abstract

Atherosclerotic cardiovascular disease (CVD), the major cause of premature human mortality, is a chronic and progressive metabolic and inflammatory disease in large- and medium-sized arteries. Mouse models are widely used to gain mechanistic insights into the pathogenesis of atherosclerosis and have facilitated the discovery of anti-atherosclerotic drugs. Despite promising preclinical studies, many drug candidates have not translated to clinical use because of the complexity of disease patho-mechanisms including lipid metabolic traits and inflammatory, genetic, and hemodynamic factors. We review the current preclinical utility and translation potential of traditional [apolipoprotein E (APOE)- and low-density lipoprotein (LDL) receptor (LDLR)-deficient mice] and emerging mouse models that include partial carotid ligation and AAV8-Pcsk9-D377Y injection in atherosclerosis research and drug discovery. This article represents an important resource in atherosclerosis research.

Keywords: atherosclerosis; inflammation; lipid metabolism; mouse model; pathology; therapeutics.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis* / genetics
  • Disease Models, Animal
  • Humans
  • Lipoproteins, LDL
  • Mice
  • Mice, Knockout
  • Proprotein Convertase 9* / genetics
  • Proprotein Convertase 9* / metabolism
  • Translational Research, Biomedical

Substances

  • Apolipoproteins E
  • Lipoproteins, LDL
  • Pcsk9 protein, mouse
  • Proprotein Convertase 9