Journal
JOURNAL OF LIPID RESEARCH
Volume 56, Issue 9, Pages 1727-1737Publisher
ELSEVIER
DOI: 10.1194/jlr.M060285
Keywords
high density lipoprotein; apolipoprotein A-I; sphingomyelin; peptides; inflammation; atherosclerosis
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Funding
- American Heart Association [13SDG17230049, R01 GM113832, R01 HL068878, R01 HL117491]
- Cellular Biotechnology Training Program [T32 GM008353]
- National Natural Science for Youth Foundation of China [81202481]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars by Shenyang Pharmaceutical University [GGJJ2014102]
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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.
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