title: 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.
authors.affiliation: Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Besler
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D008075:Lipoproteins, HDL; D009569:Nitric Oxide; D002784:Cholesterol