Title:High Density Lipoprotein – Should we Raise it?
VOLUME: 10 ISSUE: 6
Author(s):Ulf Landmesser
Affiliation:University Hospital Zurich, Cardiovascular Center, Raemistrassse 100, 8091 Zurich, Switzerland.
Keywords:High density lipoprotein, endothelium, inflammation, coronary artery disease
Abstract:Low high-density lipoprotein (HDL) cholesterol levels are associated with an increased risk of coronary artery
disease and myocardial infarction. Experimental studies have identified several potential anti-atherogenic properties of
HDL, including promotion of macrophage cholesterol efflux, endothelial nitric oxide stimulation, anti-inflammatory and
anti-thrombotic effects. These observations have lead to the important question of whether raising of HDL can reduce cardiovacular
risk. Notably, recent studies have suggested that vascular effects of HDL can be highly heterogenous and are
altered in patients with coronary disease or diabetes, that has been referred to as “HDL dysfunction”. Moreover, studies
using gene-targeted mice have indicated that genetic modifications leading to a similar increase of HDL cholesterol levels
can either reduce (i.e. apoA1 transgene overexpression) or accelerate (i.e. SR-B1 deficiency) atherosclerosis, depending
on the molecular target. These findings therefore suggest that HDL cholesterol levels alone are likely not sufficient as a
readout for the vascular effects of HDL-targeted therapeutic interventions, since both, the vascular effects of on-treatment
HDL as well as the underlying molecular mechanism used to elevate HDL cholesterol levels may represent critical determinants
of the overall vascular effects of therapeutic interventions raising HDL-cholesterol levels. In summary, low HDL
cholesterol plasma levels remain associated with an increased cardiovascular risk. However, the above findings suggest
that careful clinical trial programms are needed to determine, which HDL raising therapeutic interventions may indeed
exert vasoprotective effects.
