The dual nature of HDL: Anti-Inflammatory and pro-Inflammatory

High density lipoprotein (HDL) has long been considered a protective factor against the development of coronary heart disease. Two important roles of HDL include reverse cholesterol transport (RCT) and the modulation of inflammation. The main protein component of HDL; apolipoprotein A‐I (apo A‐I) is primarily responsible for RCT. Apo A‐I can be damaged by oxidative mechanisms, which reduce the protein's ability to promote RCT. In disease states such as diabetes, associated with a chronic acute‐phase response, HDL has been found to be dysfunctional and pro‐inflammatory. HDL cholesterol levels do not predict composition and/or function and therefore it is important to evaluate the quality and not just the quantity of HDL cholesterol when considering the risk of cardiovascular events. In clinical practice, there are currently no widely available tests for measuring the composition, functionality, and inflammatory properties of HDL. Small peptides that mimic some of the properties of apo A‐I have been shown in pre‐clinical models to improve HDL function and reduce atherosclerosis without altering HDL cholesterol levels. Clinical trials using HDL and HDL mimetics as therapeutic agents are currently underway. Results in animal studies and early clinical trials will be reviewed. © 2015 BioFactors, 41(3):153–159, 2015