biostudies-literatureKim SYAmerican Heart AssociationBLRD VAUS Department of Veterans AffairsNHLBI NIH HHSNational Institutes of HealthNIGMS NIH HHSNIH HHS2127-2142https://www.ebi.ac.uk/biostudies/studies/S-EPMC10918510biostudies-literatureUnknown18(29)Aim: The impacts of synthetic high-density lipoprotein (sHDL) phospholipid components on anti-sepsis effects were investigated. Methods: sHDL composed with ApoA-I mimetic peptide (22A) and different phosphatidylcholines were prepared and characterized. Anti-inflammatory effects were investigated in vitro and in vivo on lipopolysaccharide (LPS)-induced inflammation models. Results: sHDLs composed with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (22A-DMPC) most effectively neutralizes LPS, inhibits toll-like receptor 4 recruitment into lipid rafts, suppresses nuclear factor κB signaling and promotes activating transcription factor 3 activating. The lethal endotoxemia animal model showed the protective effects of 22A-DMPC. Conclusion: Phospholipid components affect the stability and fluidity of nanodiscs, impacting the anti-septic efficacy of sHDLs. 22A-DMPC presents the strongest LPS binding and anti-inflammatory effects in vitro and in vivo, suggesting a potential sepsis treatment.Nanomedicine (London, England)Phospholipids impact the protective effects of HDL-mimetic nanodiscs against lipopolysaccharide-induced inflammation.PMC1091851020POST3521818R35 GM141478VA I01BX004639R01GM113832, R01GM121796, T32 GM007767, T32 GM008353, T32 HL125242T32 GM008353R01 GM113832T32 HL125242I01 BX004639R01 GM121796T32 GM007767T32 GM145304Mei LOlsen KKim SYYu MXia ZLi XASchwendeman AFawaz MVMorin EEKang JfalsePhospholipids impact the protective effects of HDL-mimetic nanodiscs against lipopolysaccharide-induced inflammation.Aim: The impacts of synthetic high-density lipoprotein (sHDL) phospholipid components on anti-sepsis effects were investigated. Methods: sHDL composed with ApoA-I mimetic peptide (22A) and different phosphatidylcholines were prepared and characterized. Anti-inflammatory effects were investigated in vitro and in vivo on lipopolysaccharide (LPS)-induced inflammation models. Results: sHDLs composed with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (22A-DMPC) most effectively neutralizes LPS, inhibits toll-like receptor 4 recruitment into lipid rafts, suppresses nuclear factor κB signaling and promotes activating transcription factor 3 activating. The lethal endotoxemia animal model showed the protective effects of 22A-DMPC. Conclusion: Phospholipid components affect the stability and fluidity of nanodiscs, impacting the anti-septic efficacy of sHDLs. 22A-DMPC presents the strongest LPS binding and anti-inflammatory effects in vitro and in vivo, suggesting a potential sepsis treatment.2023-01-01T00:00:00Z2023 Dec2026-06-27T03:22:40.177Z2025-04-07T04:19:40.75ZS-EPMC109185103819737610.2217/nnm-2023-0222