title: Targeting high density lipoproteins in the prevention of cardiovascular disease?
abstract: Recent studies involving HDL-raising therapeutics have greatly changed our understanding of this field. Despite effectively raising HDL-C levels, niacin remains of uncertain clinical benefit. Synthetic niacin receptor agonists are unlikely to raise HDL-C or have other beneficial effects on plasma lipids. Despite the failure in phase 3 of 2 CETP inhibitors, 2 potent CETP inhibitors that raise HDL-C levels by >100 % (and reduce LDL-C substantially) are in late stage clinical development. Infusions of recombinant HDL containing 'wild-type' apoA-I or apoA-I Milano, as well as autologous delipidated HDL, all demonstrated promising early results, and remain in clinical development. A small molecule that causes upregulation of endogenous apoA-I production is also in clinical development. Finally, upregulation of macrophage cholesterol efflux pathways through agonism of liver X receptors or antagonism of miR-33 remains of substantial interest. The field of HDL therapeutics is poised to transition from the 'HDL-cholesterol hypothesis' to the 'HDL flux hypothesis' in which the impact on flux from macrophage to feces is deemed to be of greater therapeutic benefit than the increase in steady-state concentrations of HDL cholesterol.
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 19104, USA. dlarach@mail.med.upenn.edu
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Larach
authors.forename: Emil M
authors.initials: EM
authors.lastname: deGoma
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D016632:Apolipoprotein A-I / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008075:Lipoproteins, HDL / Q000187:drug effects* / Q000378:metabolism; D009525:Niacin / Q000627:therapeutic use*
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D009525:Niacin