HDL Apolipoprotein-Related Peptides in the Treatment of Atherosclerosis and other Inflammatory Disorders

G.      S. Getz; G.      D. Wool; C.      A. Reardon

Abstract

Elevations of HDL levels or modifying the inflammatory properties of HDL are being evaluated as possible treatment of atherosclerosis, the underlying mechanism responsible for most cardiovascular diseases. A promising approach is the use of small HDL apoprotein- related mimetic peptides. A number of peptides mimicking the repeating amphipathic α-helical structure in apoA-I, the major apoprotein in HDL, have been examined in vitro and in animal models. Several peptides have been shown to reduce early atherosclerotic lesions, but not more mature lesions unless coadminstered with statins. These peptides also influence the vascular biology of the vessel wall and protect against other acute and chronic inflammatory diseases. The biologically active peptides are capable of reducing the proinflammatory properties of LDL and HDL, likely due to their high affinity for oxidized lipids. They are also capable of influencing other processes, including ABCA1 mediated activation of JAK2 in macrophages, which may contribute to their anti-atherogenic function. The initial studies involved monomeric 18 amino acid peptides, but tandem peptides are being investigated for their anti-atherogenic and antiinflammatory properties as they more closely resemble the repeating structure of apoA-I. Peptides based on other HDL associated proteins such as apoE, apoJ and SAA have also been studied. Their mechanism of action appears to be distinct from the apoA-I based mimetics.

Keywords: Apoproteins, mimetic peptides, apoA-I, HDL, atherosclerosis, inflammation

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