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.
The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties / A. Schwendeman, D.O. Sviridov, W. Yuan, Y. Guo, E.E. Morin, Y. Yuan, J. Stonik, L. Freeman, A. Ossoli, S. Thacker, S. Killion, M. Pryor, Y..E. Chen, S. Turner, A.T. Remaley. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 56:9(2015 Sep), pp. 1727-1737.
|Titolo:||The effect of phospholipid composition of reconstituted HDL on its cholesterol efflux and anti-inflammatory properties|
|Parole Chiave:||Apolipoprotein A-I; Atherosclerosis; High density lipoprotein; Inflammation; Peptides; Sphingomyelin|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||set-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1194/jlr.M060285|
|Appare nelle tipologie:||01 - Articolo su periodico|