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Molecular dynamics simulations showed that the S1P-bound ApoM moiety in A1M efficiently activated EC surface receptors. Treatment of human umbilical vein ECs with A1M-S1P stimulated barrier function either alone or cooperatively with other barrier-enhancing molecules, including the stable prostacyclin analog iloprost, and suppressed cytokine-induced inflammation. A1M-S1P injection into mice during sterile inflammation suppressed neutrophil influx and inflammatory mediator secretion. Moreover, systemic A1M administration led to a sustained increase in circulating HDL-bound S1P and suppressed inflammation in a murine model of LPS-induced endotoxemia. We propose that A1M administration may enhance vascular endothelial barrier function, suppress cytokine storm, and promote resilience of the vascular endothelium.<\/jats:p>","DOI":"10.1126\/scisignal.adg9256","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T18:58:41Z","timestamp":1708455521000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8997-2708","authenticated-orcid":true,"given":"Yueh-Chien","family":"Lin","sequence":"first","affiliation":[{"name":"Vascular Biology Program, Boston Children\u2019s Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, 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