PXD062376

PXD062376 is an original dataset announced via ProteomeXchange.

Title	Noncanonical Caspase 4/-5 Inflammasome Activation in Coronary Artery Endothelial Cells by Lipopolysaccharides Drives Extracellular Vesicle Secretion
Description	Intestinal dysbiosis and impaired gut barrier function increase the blood bacterial lipopolysaccharide (LPS) load, referred to as endotoxemia. Endotoxemia has been implicated in cardiovascular diseases, but the underlying mechanisms are yet to be elucidated. We investigated whether intracellular LPS induces activation of the noncanonical caspase-4 and -5 inflammasome in human coronary artery endothelial cells (HCAECs) and whether this activation could mediate arterial wall inflammation. When introduced into the endothelial cell cytosol, LPS massively increased extracellular vesicle (EV)-mediated proteins secretion. The secreted proteins included biologically active kinases, transporters, transmembrane receptors, and regulators of protein synthesis. Bioinformatic analysis of the secretome data revealed increased bacterial invasion pathways, cell survival processes, and enrichment of ribosome and proteasome components upon intracellular LPS stimulation. Inhibition or depletion of the pore forming proteins Gasdermin D and MLKL reduced protein secretion. The EVs released from endothelial cells after intracellular LPS activation stimulated the expression of proinflammatory cytokines and interferon-response genes in human primary macrophages. Furthermore, intracellular LPS increased the expression of adhesion molecules and promoted monocyte attachment to HCAECs. Ultimately noncanonical inflammasome activation increased endothelial cell pyroptosis.
HostingRepository	PRIDE
AnnounceDate	2026-01-14
AnnouncementXML	Submission_2026-01-14_01:21:54.799.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tuula Nyman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-29 23:51:06	ID requested
⏵ 1	2026-01-14 01:21:55	announced

Dataset with its publication pending

submitter keyword: lipopolysaccharide, inflammation,Noncanonical inflammasome, extracellular vesicles, coronary artery disease, microbiota, caspase-4/-5, metabolic endotoksemia

Tuula Nyman
contact affiliation	Head of Proteomics University of Oslo and Oslo University Hospital
contact email	tuula.nyman@medisin.uio.no
lab head
Tuula Nyman
contact affiliation	University of Oslo
contact email	tuula.nyman@medisin.uio.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062376
     1. Label: PRIDE project
     2. Name: Noncanonical Caspase 4/-5 Inflammasome Activation in Coronary Artery Endothelial Cells by Lipopolysaccharides Drives Extracellular Vesicle Secretion