Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 2127-2142 |
| Number of pages | 16 |
| Journal | Nanomedicine |
| Volume | 18 |
| Issue number | 29 |
| DOIs | |
| State | Published - Dec 1 2023 |
Bibliographical note
Publisher Copyright:© 2024 Expert Publishing Medicine Ltd trading as Taylor & Francis.
Funding
This publication was funded by R01GM113832 (X-A Li and A Schwendeman), VA I01BX004639 (X-A Li) and R01GM121796 (X-A Li) as well as support from American Heart Association 20POST3521818 (L Mei), NIH T32 GM007767 (MV Fawaz), NIH T32 GM008353 (EE Morin), NIH T32 HL125242 (MV Fawaz and EE Morin). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Competing interests disclosure
| Funders | Funder number |
|---|---|
| National Institutes of Health (NIH) | T32 GM008353, T32 HL125242, T32 GM007767 |
| National Institutes of Health (NIH) | |
| American the American Heart Association | 20POST3521818 |
| American the American Heart Association |
Keywords
- endotoxemia
- high-density lipoproteins
- nanodiscs
- phospholipids
- sepsis
ASJC Scopus subject areas
- Bioengineering
- Medicine (miscellaneous)
- Biomedical Engineering
- General Materials Science
- Development