The role of aging on endothelial cell-cell junctions and pulmonary microvascular permeability

ABSTRACT: 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

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung, Epithelial Cell

SUBMITTER: Daniel Young  

LAB HEAD: Antoine Dufour

PROVIDER: PXD065409 | Pride | 2025-12-29

REPOSITORIES: Pride