High-density lipoprotein dysfunction in the development of cardiovascular disease and as a therapeutic target

European Coordinator:
  • Thomas LUSCHER, University of Zurich (Switzerland)
North American Coordinator:
  • Alan FOGELMAN, University of California, Los Angeles, David Geffen School of Medicine (USA)
  • John DEANFIELD, University College London (UK)
  • Stanley HAZEN, Cleveland Clinic (USA)
  • Jan Albert KUIVENHOVEN, Academic Medical Center, Amsterdam (The Netherlands)
  • Ulf LANDMESSER, Charité Universitätsmedizin Berlin (Germany)
  • Bart STAELS, Université Lille Nord de France/Institut Pasteur de Lille (France)
  • Alan TALL, Columbia University College of Physicians and Surgeons, New York (USA)

High-density lipoprotein cholesterol (HDL) has several protective effects against atherosclerosis: it promotes the outflow of cholesterol from macrophages, the immune cells that accumulate in atherosclerotic plaques; it inhibits inflammation and clotting; and it stimulates vascular repair. While one would expect that increasing the level of HDL would be an effective way to prevent and treat atherosclerosis, clinical studies of a drug developed specifically to increase HDL failed to demonstrate any benefit. One explanation for the lack of effect is that the biologic activities of HDL, rather than simply its level in the blood, contribute to its beneficial effect. Indeed, there is evidence that HDL becomes “dysfunctional” and loses its protective properties in patients with atherosclerosis.

This network aims to define the genetic variations and molecular mechanisms that lead to HDL dysfunction. An important aim of the network is to develop reliable assays to evaluate the different biological activities of HDL. These assays will allow efficient testing of new therapies targeting HDL so that experimental observations can be translated quickly to clinical application.