Impact of short-term administration of high-density lipoproteins and atorvastatin on atherosclerosis in rabbits

Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2416-21. doi: 10.1161/01.ATV.0000184760.95957.d6. Epub 2005 Sep 1.

Abstract

Objective: This study investigates effects of short-term administration of high-density lipoproteins (HDL) and a statin on atherosclerosis in cholesterol-fed rabbits. Effects of HDL apolipoprotein and phospholipid composition have also been investigated.

Methods and results: Aortic atherosclerosis was established over 17 weeks in 46 rabbits by balloon denudation and cholesterol feeding. During the past 5 days of the cholesterol-feeding period, animals received: (1) no treatment; (2) oral atorvastatin 5 mg/kg on each of the 5 days; or (3) infusions of HDL (8 mg/kg apolipoprotein A-I) on days 1 and 3 of the treatment phase. After euthanization, lesion size and composition were assessed by histological and immunohistochemical analysis. HDL (but not atorvastatin) reduced lesion size by 36% (P<0.05). The ratio of smooth muscle cells to macrophages in the lesions increased 2.6-fold in animals infused with HDL (P<0.05) and 4-fold in those receiving atorvastatin (P<0.01). HDL and atorvastatin reduced matrix metalloproteinase (MMP)-9 expression by 42% (P<0.05) and 45% (P<0.03), respectively. HDL increased thrombomodulin expression 2-fold (P<0.03). The beneficial effects on lesion area and plaque cellular composition were influenced by HDL phospholipid and apolipoprotein composition.

Conclusions: Infusing small amounts of HDL rapidly reduces lesion size and is comparable to atorvastatin in promoting a stable plaque phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Diseases / drug therapy
  • Aortic Diseases / pathology
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology*
  • Atorvastatin
  • Cholesterol, Dietary / blood
  • Cholesterol, Dietary / pharmacology
  • Drug Therapy, Combination
  • Heptanoic Acids / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / pharmacology*
  • Male
  • Pyrroles / pharmacology*
  • Rabbits

Substances

  • Cholesterol, Dietary
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, HDL
  • Pyrroles
  • Atorvastatin