The goal of this study was to understand how the reconstituted HDL (rHDL) phospholipid composition affects its cholesterol efflux and anti-inflammatory properties. 5A, an apolipoprotein A-I mimetic peptide, was combined with either sphingomyelin (SM) or palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (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-β HDL was observed following incubation o... More
The goal of this study was to understand how the reconstituted HDL (rHDL) phospholipid composition affects its cholesterol efflux and anti-inflammatory properties. 5A, an apolipoprotein A-I mimetic peptide, was combined with either sphingomyelin (SM) or palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (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-β HDL was observed following incubation of rHDLs with both human and rat plasma in vitro, with 5A-SM inducing higher extent of pre-β 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 phospholipid used to reconstitute peptide has significant influence on rHDL anti-inflammatory and anti-atherosclerosis properties.
