PXD065409

PXD065409 is an original dataset announced via ProteomeXchange.

Title	The role of aging on endothelial cell-cell junctions and pulmonary microvascular permeability
Description	Acute respiratory distress syndrome (ARDS) is a leading cause of intensive care unit (ICU) admissions and is associated with high short- and long-term mortality, particularly among elderly patients. Aging is a major risk factor for ARDS development and worsened outcomes, yet the mechanisms underlying age-related susceptibility remain poorly defined. Pulmonary microvascular endothelial cell (PMVEC) barrier dysfunction plays a central role in ARDS pathophysiology, where disruption of cell-cell junctions leads to increased vascular permeability and alveolar edema. While aging has been associated with increased microvascular permeability in several vascular beds, the specific effects of age on pulmonary endothelial cell junctions remain largely unexplored. Here, we investigated the impact of aging on PMVEC barrier function and junctional integrity under basal conditions. Using the XperT permeability assay, we demonstrate that PMVECs from aged mice exhibit significantly increased paracellular leak and disrupted VE-cadherin localization compared to those from young mice. Western blot analyses further revealed age-associated reductions in the tight junction protein claudin-5 and the adherens junction protein γ-catenin, despite an increase in VE-cadherin levels. Proteomic profiling of PMVECs uncovered broad age-related differences in pathways related to mRNA processing, protein folding, cytoskeletal regulation, and inflammation. These findings suggest that aging impairs pulmonary endothelial barrier integrity through cell junction disruption and proteome remodeling, offering mechanistic insight into the heightened vulnerability of elderly individuals to ARDS. Targeting age-associated endothelial dysfunction may represent a promising therapeutic strategy to mitigate ARDS morbidity and mortality in aging populations
HostingRepository	PRIDE
AnnounceDate	2025-12-29
AnnouncementXML	Submission_2025-12-28_16:18:48.453.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniel Young
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-24 13:34:06	ID requested
⏵ 1	2025-12-28 16:18:49	announced

Manji A, Wang L, Pape C, Mehta S, Patel P, Yeung SC, Patterson EK, Dufour A, Young D, Veldhuizen RAW, Gill SE, The role of aging on endothelial cell-cell junctions and pulmonary microvascular permeability in male mice. Physiol Rep, 13(24):e70686(2025) [pubmed]

10.14814/phy2.70686;

submitter keyword: Acute Respiratory Distress Syndrome (ARDS), Endothelial Barrier Dysfunction, Proteomics, Inflammation,Cytoskeleton, Aging

Antoine Dufour
contact affiliation	Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
contact email	Antoine.Dufour@ucalgary.ca
lab head
Daniel Young
contact affiliation	University of Calgary
contact email	daniel.young1@ucalgary.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065409
     1. Label: PRIDE project
     2. Name: The role of aging on endothelial cell-cell junctions and pulmonary microvascular permeability