Inhibition of rupture of established atherosclerotic plaques by treatment with apolipoprotein A-I

Gerrit J. Reimers, Christopher L. Jackson, Jasmine Rickards, Peter Y. Chan, Jeffrey S. Cohn, Kerry Anne Rye, Philip J. Barter, Kenneth J. Rodgers

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AimsPlasma concentrations of high-density lipoprotein (HDL)-cholesterol correlate inversely with the incidence of myocardial infarction in humans. We investigated the effect of treatment with human apolipoprotein A-I (apoA-I), the principal protein of HDL, on plaque disruption in an animal model.Methods and resultsSeventy apolipoprotein E knockout mice were induced to develop atherosclerotic lesions in the brachiocephalic artery by feeding a high-fat diet for 9 weeks. Mice then received twice-weekly treatment with human apoA-I (8 mg/kg) or vehicle, for 2 weeks. The incidence of acute plaque disruption was reduced by 65 in mice receiving apoA-I (P < 0.01). Plaques in treated mice had a more stable phenotype, with an increase in smooth muscle cell (SMC): macrophage ratio (P 0.05), principally the consequence of an increase in the number of SMC in plaques. In the fibrous cap, there were reductions in matrix metalloproteinase-13 (-69, P < 0.0001) and S100A4, a marker of SMC de-differentiation (-60, P < 0.0001). These results indicate that 2 weeks of treatment with small amounts of human apoA-I produces more stable plaques in a mouse model.ConclusionTreatment with apoA-I has the potential to stabilize plaques and prevent plaque rupture in humans.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalCardiovascular Research
Issue number1
Publication statusPublished - 1 Jul 2011
Externally publishedYes


  • Apolipoprotein A-I
  • Atherosclerosis
  • Plaque rupture
  • Smooth muscle cells

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