Vasa vasorum and plaque progression, and responses to atorvastatin in a rabbit model of atherosclerosis: contrast-enhanced ultrasound imaging and intravascular ultrasound study

Heart. 2013 Jan;99(1):48-54. doi: 10.1136/heartjnl-2012-302775. Epub 2012 Oct 25.

Abstract

Objectives: To serially investigate the relationship between vasa vasorum (VV) proliferation and plaque progression in vivo, and the effects of atorvastatin on VV and atherosclerosis as assessed by contrast-enhanced ultrasound (CEUS) and intravascular ultrasound (IVUS) imaging.

Methods: Carotid atherosclerosis was induced in rabbits with a high-cholesterol diet for 20 weeks and balloon injury. At week 16, following the imaging of the right common carotid arteries by CEUS and IVUS, 20 rabbits were randomised into a control or atorvastatin group (2 mg/kg/day). At week 20, CEUS and IVUS were repeated. Normalised maximal video-intensity enhancement (MVE) was calculated to quantify the density of VV. Plaque volume was determined by IVUS.

Results: When compared with the control group, lipid levels were not significantly lower following 4 weeks of atorvastatin administration. The increases in the normalised MVE over time were greater in the control group than in the atorvastatin group (p=0.001). The increase in plaque volume from 16 to 20 weeks was significantly greater in the control group than in the atorvastatin group (p=0.001). There was a positive relationship between changes in normalised MVE and plaque volume (r=0.72, p=0.002).

Conclusions: There was a positive correlation between VV density and plaque progression. Atorvastatin significantly inhibits the development of adventitial VV and progression of atherosclerosis independent of lowering the cholesterol level.

Publication types

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

MeSH terms

  • Animals
  • Atorvastatin
  • Carotid Artery Diseases / diagnostic imaging*
  • Carotid Artery Diseases / drug therapy
  • Carotid Artery Diseases / pathology
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Artery, Common / drug effects
  • Carotid Artery, Common / pathology
  • Cell Proliferation / drug effects
  • Contrast Media*
  • Disease Models, Animal
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Image Enhancement*
  • Male
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / drug therapy
  • Plaque, Atherosclerotic / pathology
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Rabbits
  • Ultrasonography, Interventional / methods*
  • Vasa Vasorum / diagnostic imaging*
  • Vasa Vasorum / drug effects
  • Vasa Vasorum / pathology

Substances

  • Contrast Media
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin