Fibromuscular cap composition is important for the stability of established atherosclerotic plaques in mature WHHL rabbits treated with statins

Atherosclerosis. 2001 Jul;157(1):75-84. doi: 10.1016/s0021-9150(00)00708-5.


We examined the relationship between plaque vulnerability and fibromuscular cap composition using hydrophilic pravastatin and lipophilic fluvastatin. WHHL rabbits aged 10 months were given pravastatin (50 mg/kg) or fluvastatin (20 mg/kg) for 52 weeks. The atherosclerotic lesions were immunohistochemically or conventionally stained and the components were analyzed with a color image analyzer. Compared with the control group, the plasma cholesterol levels were decreased by about 25% in both statin groups. Pravastatin decreased the lipid components (macrophages+extracellular lipids) in whole aortic plaques by 34% and the fibrous caps of coronary plaques by 55%. Fluvastatin decreased the fibromuscular components (smooth muscle cells+collagen fibers) in whole aortic plaques and in the fibromuscular caps of the aortic and coronary plaques. In the pravastatin group, the vulnerability index, the ratio of (lipid components)/(fibromuscular components), was decreased in whole aortic plaques by 28% and in the fibromuscular caps of coronary lesions by 61%, while the indexes were increased in the fluvastatin group. The incidence of vulnerable plaques was decreased by 74% in the coronary plaques of the pravastatin group. Our results suggest that the stability of atheromatous plaques was improved due to a decrease of the lipid components and vulnerability index of the fibromuscular cap by pravastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Arteriosclerosis / etiology
  • Arteriosclerosis / pathology*
  • Arteriosclerosis / prevention & control
  • Fatty Acids, Monounsaturated / pharmacology*
  • Fatty Acids, Monounsaturated / therapeutic use
  • Fluvastatin
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Muscle, Smooth, Vascular / pathology
  • Pravastatin / pharmacology*
  • Pravastatin / therapeutic use
  • Rabbits


  • Anticholesteremic Agents
  • Fatty Acids, Monounsaturated
  • Indoles
  • Fluvastatin
  • Pravastatin