Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation.

Autor: Lin YC; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Swendeman S; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Moreira IS; Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal.; CNC-Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000-456 Coimbra, Portugal., Ghosh A; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Kuo A; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Rosário-Ferreira N; CNC-Center for Neuroscience and Cell Biology, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000-456 Coimbra, Portugal., Guo S; Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115 USA., Culbertson A; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Levesque MV; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Cartier A; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Seno T; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Schmaier A; Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115 USA.; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA., Galvani S; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Inoue A; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan., Parikh SM; Division of Nephrology and Department of Medicine, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA., FitzGerald GA; Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA., Zurakowski D; Department of Anesthesia and Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Liao M; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.; Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.; Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen 518055, China., Flaumenhaft R; Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115 USA., Gümüş ZH; Department of Genetics and Genomic Sciences and Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Hla T; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Jazyk: angličtina
Zdroj: Science signaling [Sci Signal] 2024 Feb 20; Vol. 17 (824), pp. eadg9256. Date of Electronic Publication: 2024 Feb 20.
DOI: 10.1126/scisignal.adg9256
Abstrakt: High-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural protein of HDL that forms lipid nanoparticles, and ApoM, a chaperone for the bioactive lipid sphingosine 1-phosphate (S1P). A1M forms HDL-like particles, binds to S1P, and is signaling competent. 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.
Databáze: MEDLINE