Atherosclerosis and vascular disease: effects of peptide mimetics of apolipoproteins.
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.
Garber
David W
DW
Department of Medicine, the University of Alabama at Birmingham, Birmingham AL 35294, USA. dgarber@uab.edu
Handattu
Shaila P
SP
Datta
Geeta
G
Mishra
Vinod K
VK
Gupta
Himanshu
H
White
C Roger
CR
Anantharamaiah
G M
GM
D000818:Animals; D016632:Apolipoprotein A-I / Q000627:therapeutic use; D001053:Apolipoproteins / Q000737:chemistry / Q000502:physiology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use*; D011487:Protein Conformation; D014652:Vascular Diseases / Q000188:drug therapy* / Q000503:physiopathology
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008070:Lipopolysaccharides; D010455:Peptides; D002784:Cholesterol