title: Drugs in development: targeting high-density lipoprotein metabolism and reverse cholesterol transport.
abstract: OBJECTIVE
  This review summarizes currently available therapies for raising high-density lipoprotein cholesterol (HDL-C) and expands on therapies currently in development that target high-density lipoprotein cholesterol.
  
  
  RESULTS
  In the realm of new high-density lipoprotein-raising therapies, there is a strong focus on high-density lipoprotein metabolism and the reverse cholesterol transport pathway. Several infusions of recombinant apoA-I Milano/phospholipid complexes appeared to reduce atheroma volume as measured by intravascular ultrasound. Both intravenous and oral apoA-I mimetic peptides are in early clinical trials. Next generation PPAR-alpha agonists are more potent at high-density lipoprotein-raising than currently available fibrates, and dual PPAR-alpha/PPAR-gamma agonists are under investigation to help correct atherogenic dyslipidemia seen in many diabetics. Two small molecule inhibitors of the cholesteryl ester transfer protein have shown promise in clinical trials at substantially raising high-density lipoprotein cholesterol.
  
  
  CONCLUSIONS
  Larger scale clinical trials, including those with additional surrogate outcome measures as well as cardiovascular event outcomes are needed to further assess the benefit of newer high-density lipoprotein-raising therapies. Additional therapeutics are currently in development that target other parts of the reverse cholesterol transport pathway and, in addition to providing new potential pharmaceuticals, will help to further elucidate the atheroprotective mechanisms of high-density lipoprotein cholesterol.
authors.affiliation: Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Duffy
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D016632:Apolipoprotein A-I / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008954:Models, Biological; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D047493:PPAR alpha; D047495:PPAR gamma; D002784:Cholesterol