title: The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties.
abstract: The goal of this study was to understand how the reconstituted HDL (rHDL) phospholipid (PL) composition affects its cholesterol efflux and anti-inflammatory properties. An ApoA-I mimetic peptide, 5A, was combined with either SM or POPC. Both lipid formulations exhibited similar in vitro cholesterol efflux by ABCA1, but 5A-SM exhibited higher ABCG1- and SR-BI-mediated efflux relative to 5A-POPC (P < 0.05). Injection of both rHDLs in rats resulted in mobilization of plasma cholesterol, although the relative potency was 3-fold higher for the same doses of 5A-SM than for 5A-POPC. Formation of preβ HDL was observed following incubation of rHDLs with both human and rat plasma in vitro, with 5A-SM inducing a higher extent of preβ formation relative to 5A-POPC. Both rHDLs exhibited anti-inflammatory properties, but 5A-SM showed higher inhibition of TNF-α, IL-6, and IL-1β release than did 5A-POPC (P < 0.05). Both 5A-SM and 5A-POPC showed reduction in total plaque area in ApoE(-/-) mice, but only 5A-SM showed a statistically significant reduction over placebo control and baseline (P < 0.01). The type of PL used to reconstitute peptide has significant influence on rHDL's anti-inflammatory and anti-atherosclerosis properties.
authors.affiliation: Department of Medicinal Chemistry and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Anna
authors.initials: A
authors.lastname: Schwendeman
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Denis O
authors.initials: DO
authors.lastname: Sviridov
authors.affiliation: Department of Medicinal Chemistry and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Wenmin
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Cardiac Surgery, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Medicinal Chemistry and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Morin
authors.affiliation: Department of Medicinal Chemistry and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: John
authors.initials: J
authors.lastname: Stonik
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Lita
authors.initials: L
authors.lastname: Freeman
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Alice
authors.initials: A
authors.lastname: Ossoli
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Seth
authors.initials: S
authors.lastname: Thacker
authors.affiliation: KineMed, Inc., Emeryville, CA 94608.
authors.forename: Salena
authors.initials: S
authors.lastname: Killion
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Milton
authors.initials: M
authors.lastname: Pryor
authors.affiliation: Department of Cardiac Surgery, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: KineMed, Inc., Emeryville, CA 94608.
authors.forename: Scott
authors.initials: S
authors.lastname: Turner
authors.affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008075:Lipoproteins, HDL / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000008:administration & dosage; D010713:Phosphatidylcholines / Q000008:administration & dosage; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D010455:Peptides; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: apolipoprotein A-I; atherosclerosis; high density lipoprotein; inflammation; peptides; sphingomyelin