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Targeting High Density Lipoproteins in the Prevention of Cardiovascular Disease?

  • Lipid Abnormalities and Cardiovascular Prevention (G De Backer, Section Editor)
  • Published:
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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.

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Acknowledgments

This paper was supported in part by the National Center for Research Resources, Grant TL1RR024133, and is now at the National Center for Advancing Translational Sciences, Grant TL1R000138. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Disclosures

Conflicts of interest: D. B. Larach: none; E.M. deGoma: none; D.J. Rader: serves as a consultant to several companies that are developing therapies targeting HDL, including Amgen, AstraZeneca, Bristol-Myers-Squibb, CSL, Eli Lilly, Johnson & Johnson, Merck & Co, Regulus, and Novartis.

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Larach, D.B., deGoma, E.M. & Rader, D.J. Targeting High Density Lipoproteins in the Prevention of Cardiovascular Disease?. Curr Cardiol Rep 14, 684–691 (2012). https://doi.org/10.1007/s11886-012-0317-3

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