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

Stephen J. Nicholls, Belinda Cutri, Stephen G. Worthley, Patrick Kee, Kerry Anne Rye, Shisan Bao, Philip J. Barter

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132 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)2416-2421
Number of pages6
JournalArteriosclerosis, Thrombosis and Vascular Biology
Volume25
Issue number11
DOIs
Publication statusPublished - 1 Nov 2005
Externally publishedYes

Keywords

  • Atherosclerosis
  • High-density lipoprotein
  • Inflammation
  • Lipoproteins
  • Plaque stabilization

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