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


RESULTS
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.


CONCLUSIONS
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.
Navab
Mohamad
M
David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. mnavab@mednet.ucla.edu
Anantharamaiah
G M
GM
Reddy
Srinivasa T
ST
Van Lenten
Brian J
BJ
Datta
Geeta
G
Garber
David
D
Fogelman
Alan M
AM
D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy*; D008076:Cholesterol, HDL / Q000737:chemistry / Q000502:physiology; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D010455:Peptides