Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism

Curr Atheroscler Rep. 2016 Jun;18(6):29. doi: 10.1007/s11883-016-0587-0.


Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis--often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.

Keywords: Atherosclerosis; Cholesterol crystals; Inflammation; Plaque rupture; Rabbit model.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology*
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / pathology
  • Coronary Artery Disease / physiopathology*
  • Disease Models, Animal*
  • Humans
  • Inflammation / pathology
  • Myocardial Infarction / pathology
  • Plaque, Atherosclerotic / pathology*
  • Rabbits
  • Rupture, Spontaneous / etiology
  • Rupture, Spontaneous / pathology
  • Rupture, Spontaneous / physiopathology
  • Thrombosis / pathology*
  • Tunica Intima / pathology