Despite all existing pharmaceuticals aiming at effectively reducing LDL
cholesterol, the steadily increasing prevalence of coronary heart
disease (CHD) worldwide shifted focus on HDL as an alternative
therapeutic target for the treatment of CHD. Indeed, based on the
results from epidemiological studies, high HDL cholesterol (HDL-C)
levels have been traditionally associated to atheroprotection.
Therefore, current drug design considers plasma HDL-C levels as a
primary pharmacological target for combating CHD. However, this approach
does not take into consideration the fact that HDL is a rather
heterogeneous mixture of lipoprotein particles with distinct
apolipoprotein and lipid composition that dictate their atheroprotective
or proatherogenic function. This may explain why simply raising HDL-C
levels by pharmacological means has yet to yield the expected
atheroprotection in recent clinical trials. In this review we argue that
HDL particle functionality rather than HDL-C levels should be the
primary target in the rational design of new HDL-based pharmaceuticals
aiming at successfully treating CHD. (C) 2013 Elsevier Inc. All rights
reserved
