{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["van Leent MMT"],"funding":["National Heart Foundation of Australia","Courant Forschungszentrum Geobiologie, Georg-August-Universität Göttingen","NIBIB NIH HHS","NIDA NIH HHS","Teikyo University School of Medicine","NHLBI NIH HHS","ZonMw","National Institutes of Health","American Heart Association","Emissions Reduction Alberta","European Research Council","Deutsche Forschungsgemeinschaft","Horizon 2020 Framework Programme","FUNDING","Dutch Research Council (NWO)","Horizon 2020","Hartstichting"],"pagination":["eabe1433"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8209679"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(584)"],"pubmed_abstract":["Macrophages play a central role in the pathogenesis of atherosclerosis. The inflammatory properties of these cells are dictated by their metabolism, of which the mechanistic target of rapamycin (mTOR) signaling pathway is a key regulator. Using myeloid cell-specific nanobiologics in apolipoprotein E-deficient (<i>Apoe</i> <sup>-/-</sup>) mice, we found that targeting the mTOR and ribosomal protein S6 kinase-1 (S6K1) signaling pathways rapidly diminished plaque macrophages' inflammatory activity. By investigating transcriptome modifications, we identified <i>Psap</i>, a gene encoding the lysosomal protein prosaposin, as closely related with mTOR signaling. Subsequent in vitro experiments revealed that <i>Psap</i> inhibition suppressed both glycolysis and oxidative phosphorylation. Transplan"],"journal":["Science translational medicine"],"pubmed_title":["Prosaposin mediates inflammation in atherosclerosis."],"pmcid":["PMC8209679"],"funding_grant_id":["19PRE34380423","R01 DA049547","ZonMW Vici 91818622","91713324","R01 HL144072","ZonMW Vidi 91713324","R01 EB009638","91818622","R35 HL139598","CRC 1123-A5","research and innovation program (No 667837)","consolidator grant 681493","755320","2018T093","P01 HL131478","ZonMW Veni 016156059","681493","R01 HL084312","Spinoza grant","JTC2018, project MEMORY; 2018T093","R01 HL118440","CVON2012-03","JTC2018","CVON2018-27","016156059","2018T028","HHSN268201000045C","HHSN368201000045C","667837","R01 HL125703","SMIS 103587"],"pubmed_authors":["Sanchez-Gaytan BL","Perez-Medina C","van Leent MMT","Ye YX","Kluza E","Fayad ZA","Fisher EA","Joosten LAB","Nauta SA","Pasterkamp G","Klein ED","Mulder WJM","Zhang B","Netea MG","Lameijer MA","Lutgens E","Rother N","Nahrendorf M","Toner YC","Bekkering S","Malkus J","Teunissen AJP","Fay F","Wojtkiewicz G","Zhou X","van der Meel R","Beldman TJ","Li Y","Swirski FK","Duivenvoorden R","Riksen NP","Boltjes A"],"additional_accession":[]},"is_claimable":false,"name":"Prosaposin mediates inflammation in atherosclerosis.","description":"Macrophages play a central role in the pathogenesis of atherosclerosis. The inflammatory properties of these cells are dictated by their metabolism, of which the mechanistic target of rapamycin (mTOR) signaling pathway is a key regulator. Using myeloid cell-specific nanobiologics in apolipoprotein E-deficient (<i>Apoe</i> <sup>-/-</sup>) mice, we found that targeting the mTOR and ribosomal protein S6 kinase-1 (S6K1) signaling pathways rapidly diminished plaque macrophages' inflammatory activity. By investigating transcriptome modifications, we identified <i>Psap</i>, a gene encoding the lysosomal protein prosaposin, as closely related with mTOR signaling. Subsequent in vitro experiments revealed that <i>Psap</i> inhibition suppressed both glycolysis and oxidative phosphorylation. Transplan","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-05-31T05:00:14.158Z","creation":"2026-04-08T08:10:03.901Z"},"accession":"S-EPMC8209679","cross_references":{"pubmed":["33692130"],"doi":["10.1126/scitranslmed.abe1433"]}}