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Pharmacol Ther. 2016 Jan;157:28-42. doi: 10.1016/j.pharmthera.2015.10.010. Epub 2015 Nov 10.

Therapeutic applications of reconstituted HDL: When structure meets function.

Author information

1
UMR INSERM-UPMC 1166 ICAN, Pavillon Benjamin Delessert, Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. Electronic address: maryam.darabi-amin@inserm.fr.
2
UMR INSERM-UPMC 1166 ICAN, Pavillon Benjamin Delessert, Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. Electronic address: isabelle.guillas_baudouin@upmc.fr.
3
UMR INSERM-UPMC 1166 ICAN, Pavillon Benjamin Delessert, Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. Electronic address: wilfried.le_goff@upmc.fr.
4
UMR INSERM-UPMC 1166 ICAN, Pavillon Benjamin Delessert, Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. Electronic address: john.chapman@upmc.fr.
5
UMR INSERM-UPMC 1166 ICAN, Pavillon Benjamin Delessert, Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. Electronic address: anatol.kontush@upmc.fr.

Abstract

Reconstituted forms of HDL (rHDL) are under development for infusion as a therapeutic approach to attenuate atherosclerotic vascular disease and to reduce cardiovascular risk following acute coronary syndrome and ischemic stroke. Currently available rHDL formulations developed for clinical use contain apolipoprotein A-I (apoA-I) and one of the major lipid components of HDL, either phosphatidylcholine or sphingomyelin. Recent data have established that quantitatively minor molecular constituents of HDL particles can strongly influence their anti-atherogenic functionality. Novel rHDL formulations displaying enhanced biological activities, including cellular cholesterol efflux, may therefore offer promising prospects for the development of HDL-based, anti-atherosclerotic therapies. Indeed, recent structural and functional data identify phosphatidylserine as a bioactive component of HDL; the content of phosphatidylserine in HDL particles displays positive correlations with all metrics of their functionality. This review summarizes current knowledge of structure-function relationships in rHDL formulations, with a focus on phosphatidylserine and other negatively-charged phospholipids. Mechanisms potentially underlying the atheroprotective role of these lipids are discussed and their potential for the development of HDL-based therapies highlighted.

KEYWORDS:

Cardiovascular disease; Functionality; High density lipoprotein; Lipidomics; Synthetic HDL; rHDL

[Indexed for MEDLINE]

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