Targeting cholesterol crystal-induced inflammation for the secondary prevention of cardiovascular disease

J Cardiovasc Pharmacol Ther. 2014 Jan;19(1):45-52. doi: 10.1177/1074248413499972. Epub 2013 Sep 13.

Abstract

Cholesterol crystals are present in nascent and advanced atherosclerotic plaque. Under some conditions, they may enlarge and cause direct plaque trauma or trigger an inflammatory cascade that promotes the growth and instability of atherosclerotic plaque. Therapies that reduce the risk of cholesterol crystal formation or prevent the associated inflammatory response have the potential to improve the clinical outcome of patients with cardiovascular disease. Statins have pleiotropic effects that can reduce the size of the free cholesterol pool contained within atherosclerotic plaques and prevent the formation of cholesterol crystals. Colchicine prevents crystal-induced inflammation by virtue of its ability to inhibit macrophage and neutrophil function. Both statins and colchicine have been demonstrated to reduce the risk of cardiovascular events in patients with stable coronary disease. The efficacy of statins and colchicine for cardiovascular prevention supports the hypothesis that crystal-induced inflammation plays an integral role in the progression and instability of coronary disease. Inhibition of cholesterol crystal-induced inflammation offers a promising new target for the secondary prevention of cardiovascular disease.

Keywords: atherosclerosis; heart disease; ischemic.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol / chemistry*
  • Colchicine / pharmacology
  • Colchicine / therapeutic use
  • Crystallization
  • Disease Progression
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Molecular Targeted Therapy
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Plaque, Atherosclerotic / drug therapy
  • Plaque, Atherosclerotic / pathology
  • Secondary Prevention / methods

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol
  • Colchicine