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.
Highlights
The goal of this study was to understand how the reconstituted HDL phospholipid (PL) composition affects its cholesterol efflux and anti-inflammatory properties
We found that 5A-SM effluxes more cholesterol by SR-BI and ABCG1 mechanisms relatively to 5A-POPC, and this ability is translated to greater cholesterol efflux capacity by plasma following infusion of reconstituted HDL (rHDL)
The cholesterol efflux following addition of 5APOPC and 5A-SM rHDLs to human and rat plasma resulted in lipoprotein remodeling with notable formation of pre HDL particles
Summary
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 5APOPC (P < 0.05). 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 antiinflammatory properties, but 5A-SM showed higher inhibition of TNF-␣, IL-6, and IL-1 release than did 5A-POPC (P < 0.05).
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