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Mechanisms of Disease: HDL metabolism as a target for novel therapies

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 102–109 (2007)Cite this article

Abstract

Plasma concentrations of HDL cholesterol are inversely correlated with risk of coronary heart disease, and low HDL-cholesterol levels are a risk factor even in patients aggressively treated for LDL reduction. Thus, there is great interest in targeting HDL cholesterol therapeutically. The existing approaches are limited in their ability to raise HDL-cholesterol levels, and there has, therefore, been a major focus on the development of novel therapies. The goal of new approaches is to either raise HDL-cholesterol levels or improve the function of HDL. Here, the current status of the development of novel therapies targeted toward HDL metabolism is reviewed.

Key Points

  • Current clinical approaches to treating low HDL-cholesterol levels are inadequate and new therapies are needed that either increase HDL-cholesterol levels or improve HDL function

  • HDL protects against atherosclerosis by promoting the process of reverse cholesterol transport, as well as potentially through additional mechanisms such as anti-inflammatory, antioxidative, antithrombotic, and nitric-oxide-promoting properties

  • Promotion of macrophage cholesterol efflux is a desirable target for development of novel therapies and might be achieved through targeting the liver X receptor or the peroxisome proliferative activated receptors

  • Apolipoprotein A-I mimetic peptides present a potential biological method for increasing HDL function as an approach to reducing atherosclerosis

  • The effect of a novel therapeutic approach on the plasma HDL-cholesterol level alone is not an adequate predictor of the potential clinical benefit

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  1. Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA rader@mail.med.upenn.edu

Authors and Affiliations

  1. DJ Rader is the Cooper-McClure Professor of Medicine, Pathology, and Pharmacology at the University of Pennsylvania School of Medicine, Philadelphia, PA, USA.,

    Daniel J Rader

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Competing interests

Dr Rader has interactions with companies that are involved in discovering new therapies targeted to HDL. He has received grant/research support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Bruin Pharma, GlaxoSmithKline, KOS Pharmaceuticals, Merck and Co., Pfizer, Schering-Plough and Takeda.

He is/has been a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, KOS Pharmaceuticals, Merck and Co., Merck–Schering Plough, Pfizer, Reliant, sanofi-aventis, Schering-Plough, Takeda and Wyeth.

He has been on the speakers bureau/received honoraria from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, KOS Pharmaceuticals, Merck and Co., Merck–Schering Plough, Pfizer, Reliant, sanofi-aventis, Schering-Plough, Takeda and Wyeth.

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Rader, D. Mechanisms of Disease: HDL metabolism as a target for novel therapies. Nat Rev Cardiol 4, 102–109 (2007). https://doi.org/10.1038/ncpcardio0768

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