Molecular mechanisms of vascular effects of High‐density lipoprotein: alterations in cardiovascular disease

Abstract

Low high‐density lipoprotein (HDL)‐cholesterol levels are associated with an increased risk of coronary artery disease (CAD) and myocardial infarction, which has triggered the hypothesis that HDL, in contrast to low‐density lipoprotein (LDL), acts as an anti‐atherogenic lipoprotein. Moreover, experimental studies have identified potential anti‐atherogenic properties of HDL, including promotion of macrophage cholesterol efflux and direct endothelial‐protective effects of HDL, such as stimulation of endothelial nitric oxide production and repair, anti‐apoptotic, anti‐inflammatory and anti‐thrombotic properties. Studies in gene‐targeted mice, however, have also indicated that increasing HDL‐cholesterol plasma levels can either limit (e.g. apolipoprotein A‐I) or accelerate (e.g. Scavenger receptor class B type I) atherosclerosis. Moreover, vascular effects of HDL have been observed to be heterogenous and are altered in patients with CAD or diabetes, a condition that has been termed ‘HDL dysfunction’. These alterations in biological functions of HDL may need to be taken into account for HDL‐targeted therapies and considering raising of HDL‐cholesterol levels alone is likely not sufficient in this respect. It will therefore be important to further determine, which biological functions of HDL are critical for its anti‐atherosclerotic properties, as well as how these can be measured and targeted.