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Current Vascular Pharmacology

Volume 10 Issue 6
ISSN: 1570-1611
eISSN: 1875-6212

 

   All Titles

  High Density Lipoprotein - Should we Raise it?
  pp.718-719 (2) Author: Ulf Landmesser
 
 
      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.

 
  Keywords: High density lipoprotein, endothelium, inflammation, coronary artery disease
  Affiliation: University Hospital Zurich, Cardiovascular Center, Raemistrassse 100, 8091 Zurich, Switzerland.
 
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