PXD068978
PXD068978 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Cholesterol binding to VCAM-1 promotes vascular inflammation |
| Description | 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-09-29 |
| AnnouncementXML | Submission_2025-09-29_19:40:53.017.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Andrew Becker |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-09-29 19:12:12 | ID requested | |
| ⏵ 1 | 2025-09-29 19:40:53 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Cholesterol, VCAM-1, accessible cholesterol, Aster, immune response, endothelial, DatasetType:Proteomics |
Contact List
| Peter Tontonoz | |
|---|---|
| contact affiliation | University of California Los Angeles |
| contact email | ptontonoz@mednet.ucla.edu |
| lab head | |
| Andrew Becker | |
| contact affiliation | UCLA |
| contact email | abpalmer@g.ucla.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v11/MSV000099325/ |
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