Atherosclerotic Plaque Destabilization in Mice: A Comparative Study

PLoS One. 2015 Oct 22;10(10):e0141019. doi: 10.1371/journal.pone.0141019. eCollection 2015.

Abstract

Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

Publication types

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

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / pathology*
  • Carotid Artery, Common / pathology
  • Carotid Artery, Common / surgery
  • Diet, High-Fat
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Hypercholesterolemia / pathology*
  • Hypertension, Renovascular / pathology*
  • Male
  • Mice
  • Mice, Knockout
  • Plaque, Atherosclerotic / classification
  • Plaque, Atherosclerotic / pathology*
  • Renal Artery / pathology
  • Renal Artery / surgery
  • Stress, Mechanical

Substances

  • Apolipoproteins E

Grants and funding

The research was supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VIDI project 91712303), the Deutsche Forschungsgemeinschaft (DFG) (SO876/6-1, SFB1123 TP A06 and B05), and the LMU excellent program.