• Open Access

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

Authors

  • Christian Besler,

    1. Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
    2. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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  • Thomas F. Lüscher,

    1. Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
    2. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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  • Ulf Landmesser

    Corresponding author
    1. Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
    2. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    • Tel: +41 44 255 9595; Fax: +41 44 255 4251

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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.

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