HDL-replacement therapy: mechanism of action, types of agents and potential clinical indications

Abstract

HDL-replacement therapy is a promising new treatment strategy involving the acute administration of HDL to rapidly stabilize patients at imminent risk for developing a myocardial infarction, such as those with acute coronary syndrome. This review will first focus on the anti-atherogenic mechanisms for HDL, such as the stimulation of the reverse cholesterol transport pathway, and then discuss the other potential beneficial biological effects of HDL on atherosclerosis. The various types of HDL-replacement therapies that are being investigated and developed will be reviewed and ongoing clinical trials and other possible clinical indications for HDL-replacement therapy besides the prevention of myocardial infarction will also be described. Finally, HDL-replacement therapy will be put into perspective by summarizing the current gaps in our knowledge of HDL metabolism and identifying challenges for future research in this area.

Figure 1. Reverse cholesterol transport pathway

ApoA-I acquires lipid in the liver and intestine to form nascent discoidal shaped HDL. This form of HDL can then efflux cholesterol from peripheral cells and return it back to the liver for excretion into the bile. This can occur either by hepatic uptake by SR-BI or by uptake of LDL after cholesteryl esters are transferred to LDL from HDL by CETP. ABCA1: ATP-binding cassette transporter A–I; ApoA-I: Apolipoprotein A–I; CE: Cholesteryl esters; CETP: Cholesteryl ester transfer protein; LCAT: Lecithin:cholesterol acyltransferase; LDLR: LDL receptor; SR-BI: Scavenger receptor B–I; TG: Trigylcerides.