The plasma lipoproteins are particles made up of proteins and lipids that carry fat through the bloodstream to various parts of the body. Evidence is clear that levels of the various types of lipoproteins (HDL, LDL, IDL and VLDL) have considerable influence on an individual's chances of developing atherosclerosis. Certain lipoproteins, particularly LDL, have an unfavorable influence, whereas certain others, particularly HDL, have a favorable influence. One of the goals of drug prevention of atherosclerosis is to lower LDL while raising HDL. While LDL can be lowered significantly by a number of drugs, HDL has generally proved refractory to drug therapy and in many instances actually increases. It is thought that LDL serves to deliver cholesterol to cells of the body, such as artery wall cells where buildup of cholesterol is responsible for atherosclerosis, and that HDL serves to remove cholesterol from cells in a process called reverse cholesterol transport. The protective effect of HDL, as well as its reverse cholesterol transport activity, appears to be tied to the level of LCAT activating activity of apolipoprotein A-I in HDL. We propose that synthetic analogs of the amphipathic peptides can be used to increase reverse cholesterol transport by raising or supplementing HDL via peptide injection into the blood stream. This increase in reverse cholesterol transport may serve to prevent or reverse atherosclerosis in patients at high risk.
