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

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.

• Authors: David W Garber, Shaila P Handattu, Geeta Datta, Vinod K Mishra, Himanshu Gupta, C Roger White, G M Anantharamaiah
• Journal: Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 7 Issue 4 Pg. 235-40 (Aug 2006) ISSN: 1389-2010 [Print] Netherlands
• PMID: 16918400 (Publication Type: Journal Article, Review)

Chemical References

• Apolipoprotein A-I
• Apolipoproteins
• Cholesterol, HDL
• Lipopolysaccharides
• Peptides
• Cholesterol

Topics

• Animals
• Apolipoprotein A-I (therapeutic use)
• Apolipoproteins (chemistry, physiology)
• Atherosclerosis (drug therapy, physiopathology)
• Cholesterol (metabolism)
• Cholesterol, HDL (metabolism)
• Coronary Disease (drug therapy)
• Humans
• Lipopolysaccharides (chemistry, pharmacology)
• Mice
• Mice, Inbred C57BL
• Molecular Mimicry
• Peptides (pharmacology, therapeutic use)
• Protein Conformation
• Vascular Diseases (drug therapy, physiopathology)