Novel HDL-directed pharmacotherapeutic strategies

Nat Rev Cardiol. 2011 May;8(5):266-77. doi: 10.1038/nrcardio.2010.200. Epub 2011 Jan 18.


The burden of atherothrombotic cardiovascular disease remains high despite currently available optimum medical therapy. To address this substantial residual risk, the development of novel therapies that attempt to harness the atheroprotective functions of HDL is a major goal. These functions include the critical role of HDL in reverse cholesterol transport, and its anti-inflammatory, antithrombotic, and antioxidant activities. Discoveries in the past decade have shed light on the complex metabolic and antiatherosclerotic pathways of HDL. These insights have fueled the development of HDL-targeted drugs, which can be classified among four different therapeutic approaches: directly augmenting apolipoprotein A-I (apo A-I) levels, such as with apo A-I infusions and upregulators of endogenous apo A-I production; indirectly augmenting apo A-I and HDL-cholesterol levels, such as through inhibition of cholesteryl ester transfer protein or endothelial lipase, or through activation of the high-affinity niacin receptor GPR109A; mimicking the functionality of apo A-I with apo A-I mimetic peptides; and enhancing steps in the reverse cholesterol transport pathway, such as via activation of the liver X receptor or of lecithin-cholesterol acyltransferase.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apolipoprotein A-I / blood
  • Apolipoprotein A-I / therapeutic use
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, HDL / blood
  • Dyslipidemias / blood
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy*
  • Humans
  • Hypolipidemic Agents / therapeutic use*
  • Lipid Metabolism / drug effects
  • Molecular Mimicry
  • Treatment Outcome


  • APOA1 protein, human
  • Apolipoprotein A-I
  • Biomarkers
  • Cholesterol, HDL
  • Hypolipidemic Agents