| Autor: |
Yu M; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States., Dorsey KH; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States., Halseth T; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States., Schwendeman A; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.; Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States. |
| Abstrakt: |
Phosphatidylserine (PS) is an anionic phospholipid component in endogenous high-density lipoprotein (HDL). With the intrinsic anti-inflammatory effects of PS and the correlation between PS content and HDL functions, it was hypothesized that incorporating PS would enhance the therapeutic effects of HDL mimetic particles. To test this hypothesis, a series of synthetic high-density lipoproteins (sHDLs) were prepared with an apolipoprotein A-I (ApoA-1) mimetic peptide, 1-palmitoyl-2-oleoyl- glycero -3-phosphocholine (POPC), and 1-palmitoyl-2-oleoyl- glycero -3-phospho-l-serine (POPS). Incorporating PS was found to improve the particle stability of sHDLs. Moreover, increasing the PS content in sHDLs enhanced the anti-inflammatory effects on lipopolysaccharide-activated macrophages and endothelial cells. The incorporation of PS had no negative impact on cholesterol efflux capacity, in vivo cholesterol mobilization, and did not affect the pharmacokinetic profiles of sHDLs. Such results suggest the therapeutic potential of PS-containing sHDLs for inflammation resolution in atherosclerosis and other inflammatory diseases. |
