Apolipoprotein A-I Mimetic Peptides for the Treatment of Coronary Artery Disease

High density lipoprotein (HDL) plays a critical physiological role in protecting the body against atherosclerosis by facilitating reverse cholesterol transport and the removal of oxidized phosphoplipids from artery walls. Apolipoprotein A-I (apoA-I) is the principal protein component of HDL that is responsible for these atheroprotective effects. We have developed an apoA-I peptide analog called D-4F, which mimics the properties of apoA-I. D-4F is synthesized from Damino acids and thus can be administered orally. In murine models of atherosclerosis, D-4F markedly reduced atherosclerotic lesions in the absence of significant changes in total plasma cholesterol or HDL cholesterol levels. These results suggested that raw values of lipoprotein quantity are not the only indicators of atherosclerotic risk; the quality of the circulating lipoproteins is also important. As atherogenesis has been shown to be strongly linked to the presence of pro-inflammatory HDL, D-4F suggests therapeutic potential for treating atherosclerosis by improving the quality of patients' HDL (i.e. converting pro-inflammatory HDL to anti-inflammatory HDL in vitro). ApoA-I mimetic peptides may also prove helpful in treating other symptoms of atherosclerosis, such as endothelial dysfunction and abnormal vasorelaxation. ApoA-I mimetic peptides like D-4F indicate much promise for becoming yet another part of achieving greater cardiovascular health.