title: Therapeutic applications of reconstituted HDL: When structure meets function.
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.
authors.affiliation: 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.
authors.forename: Maryam
authors.initials: M
authors.lastname: Darabi
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guillas-Baudouin
authors.affiliation: 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.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.affiliation: 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.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: 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.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
mesh_terms: D000818:Animals; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000627:therapeutic use*; D010743:Phospholipids / Q000032:analysis / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D008075:Lipoproteins, HDL; D010743:Phospholipids
keywords: Cardiovascular disease; Functionality; High density lipoprotein; Lipidomics; Synthetic HDL; rHDL