Apolipoprotein A-I (apoA-I) mimetic peptides resemble the physiochemical properties of the helices of apoA-I and show promise for the treatment of atherosclerotic vascular diseases and other chronic inflammatory disorders. These peptides have numerous properties, such as the ability to remodel high-density lipoprotein, sequester oxidized lipids, promote cholesterol efflux, and activate an anti-inflammatory process in macrophages, any or all of which may contribute to their antiatherogenic properties. In murine models, the 4F peptide attenuates early atherosclerosis but seems to require the addition of statins to influence more mature lesions. A recently developed method for the oral delivery of the peptides that protects them from proteolysis will facilitate further research on the mechanism of action of these peptides. This review focuses on the properties of the 4F peptide, although numerous apoA-I mimetics are under investigation and a single "best" peptide that mimics all of the properties of the antiatherogenic protein apoA-I has not been identified.
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