Antiatherogenic functionality of high density lipoprotein: how much versus how good.

Plasma concentration of high density lipoprotein (HDL) is one of the most reliable negative risk factors for CVD. There is however convincing experimental and clinical evidence that plasma concentration of HDL does not convey the full picture of atheroprotective properties of HDL. HDL functionality, i.e. the ability of HDL to perform its many atheroprotective functions, is partly independent of HDL concentration and may be as important, if not more important, in determining the atheroprotective capacity of HDL. The capacity of HDL to support cholesterol efflux, its anti-inflammatory, anti-oxidant, anti-thrombotic and other atheroprotective functions are affected dramatically in conditions like coronary artery disease, chronic and acute inflammation, diabetes as well as through various interventions. The mechanisms connecting changes in HDL functionality to HDL structure are only beginning to emerge. Modifications of HDL proteins and lipids, such as advanced glycation and oxidation, changes in HDL composition and size of HDL particles, changes in abundance of various proteins and lipids carried by HDL are among factors affecting HDL functionality. A single common denominator reflecting the multiple HDL functions is yet to be found and may not exist leaving direct measurements of each HDL function as the way to assess atheroprotective capacity of HDL.