{"doi":"10.1101/2024.09.17.613543","title":"Cholesterol binding to VCAM-1 promotes vascular inflammation","abstract":"Abstract Hypercholesterolemia has long been implicated in endothelial cell (EC) dysfunction, but the mechanisms by which excess cholesterol causes vascular pathology are incompletely understood. Here we used a cholesterol-mimetic probe to map cholesterol-protein interactions in primary human ECs and discovered that cholesterol binds to and stabilizes the adhesion molecule VCAM-1. We show that accessible plasma membrane (PM) cholesterol in ECs is acutely responsive to inflammatory stimuli and that the nonvesicular cholesterol transporter Aster-A regulates VCAM-1 stability in activated ECs by controlling the size of this pool. Deletion of Aster-A in ECs increases VCAM-1 protein, promotes immune cell recruitment to vessels, and impairs pulmonary immune homeostasis. Conversely, depleting cholesterol from the endothelium in vivo dampens VCAM-1 induction in response to inflammatory stimuli. These findings identify cholesterol binding to VCAM-1 as a key step during EC activation and provide a biochemical explanation for the ability of excess membrane cholesterol to promote immune cell recruitment to the endothelium.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488983,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1201013,"name":"Xiao Xu","orcid":"0000-0002-2761-2811","position":1,"is_corresponding":false},{"id":367553,"name":"Yajing Gao","orcid":"0000-0002-8836-4452","position":2,"is_corresponding":false},{"id":1333892,"name":"Su Min Kim","orcid":"0000-0002-2280-1605","position":3,"is_corresponding":false},{"id":872783,"name":"Soon‐Gook Hong","orcid":"0000-0002-1385-4430","position":4,"is_corresponding":false},{"id":868700,"name":"Miranda Villanueva","orcid":"0000-0002-4892-8356","position":5,"is_corresponding":false},{"id":343697,"name":"Alessandra Ferrari","orcid":"0000-0001-7354-9895","position":6,"is_corresponding":false},{"id":1334387,"name":"Lauri Vanharanta","orcid":null,"position":7,"is_corresponding":false},{"id":897004,"name":"Alexander Nguyen","orcid":"0000-0001-6578-3454","position":8,"is_corresponding":false},{"id":107848,"name":"Rohith T. Nagari","orcid":"0000-0002-0677-3237","position":9,"is_corresponding":false},{"id":995433,"name":"Nikolas R. Burton","orcid":"0000-0003-2887-8846","position":10,"is_corresponding":false},{"id":1028957,"name":"Marcus J. Tol","orcid":null,"position":11,"is_corresponding":false},{"id":1327108,"name":"Andrew P. Becker","orcid":null,"position":12,"is_corresponding":false},{"id":141871,"name":"Min Jae Lee","orcid":"0000-0002-3252-6467","position":13,"is_corresponding":false},{"id":98145,"name":"Elina Ikonen","orcid":"0000-0001-8382-1135","position":14,"is_corresponding":false},{"id":377194,"name":"Keriann M. Backus","orcid":"0000-0001-8541-1404","position":15,"is_corresponding":false},{"id":564715,"name":"Julia J. Mack","orcid":"0000-0002-9239-8436","position":16,"is_corresponding":false},{"id":246036,"name":"Peter Tontonoz","orcid":"0000-0003-1259-0477","position":17,"is_corresponding":false},{"id":343699,"name":"John P. Kennelly","orcid":"0000-0002-4399-3976","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:23.929823Z","pmid":"39345495","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":[]}