Therapeutic applications of reconstituted HDL: When structure meets function

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• 作者：Maryam Darabi ; ^{maryam.darabi-amin@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Isabelle Guillas-Baudouin ^{isabelle.guillas_baudouin@upmc.fr" class="auth_mail" title="E-mail the corresponding author} ; Wilfried Le Goff ^{wilfried.le_goff@upmc.fr" class="auth_mail" title="E-mail the corresponding author} ; M. John Chapman ^{john.chapman@upmc.fr" class="auth_mail" title="E-mail the corresponding author} ; Anatol Kontush ; ^{anatol.kontush@upmc.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cardiovascular disease ; Functionality ; High density lipoprotein ; Lipidomics ; rHDL ; Synthetic HDL
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：157
• 期：Complete
• 页码：28-42
• 全文大小：998 K

文摘

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.