Phospholipids impact the protective effects of HDL-mimetic nanodiscs against lipopolysaccharide-induced inflammation.
Sang Yeop KimJukyung KangMaria V FawazMinzhi YuZiyun XiaEmily E MorinLing MeiKarl OlsenXiang-An LiAnna A SchwendemanPublished in: Nanomedicine (London, England) (2024)
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.
Keyphrases
- binding protein
- inflammatory response
- toll like receptor
- lps induced
- lipopolysaccharide induced
- nuclear factor
- high density
- fatty acid
- acute kidney injury
- signaling pathway
- transcription factor
- oxidative stress
- septic shock
- intensive care unit
- atomic force microscopy
- dna binding
- human health
- combination therapy
- risk assessment
- climate change
- smoking cessation