Human apolipoprotein A-I and A-I mimetic peptides: potential for atherosclerosis reversal

Curr Opin Lipidol. 2004 Dec;15(6):645-9. doi: 10.1097/00041433-200412000-00004.


Purpose of review: Recent publications related to the potential use of apolipoprotein (apo)A-I and apoA-I mimetic peptides in the treatment of atherosclerosis are reviewed.

Recent findings: A preliminary report indicating that infusion of apoA-IMilano into humans once weekly for 5 weeks caused a significant decrease in coronary artery atheroma volume has sparked great interest in the potential therapeutic use of apoA-I. Recent studies have revealed that HDL quality (e.g. HDL apolipoprotein and lipid content, including oxidized lipids, particle size and electrophoretic mobility, associated enzymatic activities, inflammatory/anti-inflammatory properties, and ability to promote cholesterol efflux) may be more important than HDL-cholesterol levels. Therefore, when developing new strategies to raise HDL-cholesterol concentrations by interfering with HDL metabolism, one must consider the quality of the resulting HDL. In animal models, raising HDL-cholesterol levels by administering oral phospholipids improved both the quantity and quality of HDL and was associated with lesion regression. An apoA-I mimetic peptide, namely 4F synthesized from D-amino acids (D-4F), administered orally to mice did not raise HDL-cholesterol concentrations but promoted the formation of pre-beta HDL containing increased paraoxonase activity, resulting in significant improvements in HDL's anti-inflammatory properties and ability to promote cholesterol efflux from macrophages in vitro. Oral D-4F also promoted reverse cholesterol efflux from macrophages in vivo.

Summary: The quality of HDL may be more important than HDL-cholesterol levels. ApoA-I and apoA-I mimetic peptides appear to have significant therapeutic potential in atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apolipoprotein A-I / administration & dosage
  • Apolipoprotein A-I / chemistry
  • Apolipoprotein A-I / therapeutic use*
  • Arteriosclerosis / drug therapy*
  • Cholesterol, HDL / chemistry
  • Cholesterol, HDL / physiology
  • Humans
  • Mice
  • Molecular Mimicry
  • Peptides / chemistry
  • Peptides / pharmacology
  • Peptides / therapeutic use*


  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Peptides