{"doi":"10.1101/2022.02.14.480375","title":"Engineered high-density lipoprotein particles that chaperone bioactive lipid mediators to combat endothelial dysfunction and thromboinflammation","abstract":"Abstract High-density lipoprotein (HDL) particles suppress inflammation-induced tissue injury via vascular and myeloid cell-dependent mechanisms. As such, HDL-associated bioactive lipids such as sphingosine 1-phosphate (S1P) and prostacyclin (PGI 2 ) signal via their respective G protein-coupled receptors on target cells to promote vascular endothelial function and suppress platelet and myeloid-dependent pathophysiology. Here we have constructed a fusion protein of apolipoprotein A1 (ApoA1) and apolipoprotein M (ApoM) (A1M) that forms HDL-like particles and chaperones S1P and Iloprost, stable PGI 2 analog. The A1M/S1P complex activates S1P receptor-1 (S1PR1) as a Gα i -biased agonist and attenuates the inflammation-induced NFκB pathway while A1M/Iloprost acts via IP receptor to inhibit platelet aggregation and promote endothelial barrier function. In addition to enhancing the endothelial barrier, A1M/S1P suppresses neutrophil influx, oxidative burst and inflammatory mediator secretion in a sterile inflammation model. We propose that A1M could be useful as a therapeutic to induce S1P and PGI 2 -dependent anti-inflammatory functions and suppress collateral tissue injury.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302726,"datarank":0.11659821163893086,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.012626134554939055,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.012626134554939055,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":404234,"name":"Daniel W. Lin","orcid":"0000-0002-2135-1534","position":1,"is_corresponding":false},{"id":271136,"name":"Shihui Guo","orcid":"0000-0002-0542-1221","position":2,"is_corresponding":false},{"id":315388,"name":"Alan Culbertson","orcid":"0000-0003-0166-4936","position":3,"is_corresponding":false},{"id":534845,"name":"Andrew Kuo","orcid":"0000-0002-7263-8658","position":4,"is_corresponding":false},{"id":985831,"name":"Michel V. Levesque","orcid":"0009-0004-2794-3583","position":5,"is_corresponding":false},{"id":994917,"name":"Andréane Cartier","orcid":"0000-0003-0454-0699","position":6,"is_corresponding":false},{"id":994918,"name":"Takahiro Seno","orcid":"0000-0003-4070-307X","position":7,"is_corresponding":false},{"id":656977,"name":"Alec A. Schmaier","orcid":"0000-0002-4975-700X","position":8,"is_corresponding":false},{"id":995220,"name":"Sylvain Galvani","orcid":null,"position":9,"is_corresponding":false},{"id":255551,"name":"Asuka Inoue","orcid":"0000-0003-0805-4049","position":10,"is_corresponding":false},{"id":268732,"name":"Samir M. Parikh","orcid":"0000-0002-1038-981X","position":11,"is_corresponding":false},{"id":34970,"name":"Garret A. FitzGerald","orcid":"0000-0002-5885-6819","position":12,"is_corresponding":false},{"id":240041,"name":"Maofu Liao","orcid":"0000-0002-3481-450X","position":13,"is_corresponding":false},{"id":271137,"name":"Robert Flaumenhaft","orcid":"0000-0001-8004-9688","position":14,"is_corresponding":false},{"id":260732,"name":"Timothy Hla","orcid":"0000-0001-8355-4065","position":15,"is_corresponding":false},{"id":994916,"name":"Steven Swendeman","orcid":"0000-0001-7818-4151","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:20.348385Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}