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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 pre? HDL was observed following incubation of rHDLs with both human and rat plasma in vitro, with 5A-SM inducing a higher extent of pre? formation relative to 5A-POPC. Both rHDLs exhibited anti-inflammatory properties, but 5A-SM showed higher inhibition of TNF-?, IL-6, and IL-1? 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.

SUBMITTER: Schwendeman A 

PROVIDER: S-EPMC4548777 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties.

Schwendeman Anna A   Sviridov Denis O DO   Yuan Wenmin W   Guo Yanhong Y   Morin Emily E EE   Yuan Yue Y   Stonik John J   Freeman Lita L   Ossoli Alice A   Thacker Seth S   Killion Salena S   Pryor Milton M   Chen Y Eugene YE   Turner Scott S   Remaley Alan T AT  

Journal of lipid research 20150627 9


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 th  ...[more]

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