Atherosclerosis and vascular disease: effects of peptide mimetics of apolipoproteins.

Academic Article

Abstract

  • Levels of high density lipoprotein (HDL) and its major protein component, apolipoprotein (apo) A-I, are strongly inversely correlated to risk of atherosclerosis and other vascular diseases. A number of properties of apo A-I may contribute to this protection, including removal of cholesterol from peripheral tissues to the liver (reverse cholesterol transport), anti-inflammatory and anti-oxidative activities, and modulation of vascular function. Apo A-I has lipid-associating domains that form class A amphipathic helices. Peptide analogs that have no sequence homology to the domains in apo A-I but possess the class A motif have been shown to not only associate with phospholipid but also mimic several of the functional properties of apo A-I. Peptide 4F, with four phenylalanines on the non-polar face, was found to be maximally effective in mimicking the positive qualities of apo A-I; this peptide inhibited atherosclerosis, reduced inflammation and oxidation, and improved vascular function in a number of animal models, and when synthesized with D-amino acids is orally bioavailable. Several other classes of peptide mimetics are now being studied, and may contribute to our understanding of the functions of apo E and apo J. The use of peptide mimetics to study apolipoprotein function has proved to be a powerful tool, and may lead to novel therapeutic agents in the prevention of atherosclerosis and other vascular diseases.
  • Published In

    Keywords

  • Animals, Apolipoprotein A-I, Apolipoproteins, Atherosclerosis, Cholesterol, Cholesterol, HDL, Coronary Disease, Humans, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Molecular Mimicry, Peptides, Protein Conformation, Vascular Diseases
  • Author List

  • Garber DW; Handattu SP; Datta G; Mishra VK; Gupta H; White CR; Anantharamaiah GM
  • Start Page

  • 235
  • End Page

  • 240
  • Volume

  • 7
  • Issue

  • 4