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Updated: Jan 8, 2026
Author Spotlight: Advances in Quantifying Microvascular Density in Aging Murine Lungs
Published on: January 3, 2025
The role of aging on endothelial cell-cell junctions and pulmonary microvascular permeability in male mice
Aminmohamed Manji1,2, Lefeng Wang1,3, Cynthia Pape1,3
1Centre for Critical Illness Research, London Health Sciences Centre Research Institute, London, Ontario, Canada.
Abstract:
Pulmonary microvascular endothelial cell (PMVEC) intercellular junctions are critical for maintaining barrier function and mitigating pulmonary edema. Previously, we demonstrated that aging exacerbated pulmonary microvascular permeability in a model of lung injury. Based on this, we hypothesized that aging was associated with increased PMVEC barrier dysfunction due to impaired cell-cell junction integrity. PMVEC were isolated from young and aged mice and cultured to confluence in vitro. Barrier function, junctional integrity, alterations in the proteome, markers of inflammation, and actin cytoskeleton organization were all assessed. To model injurious conditions, PMVEC were stimulated with inflammatory cytokines. PMVEC from aged mice exhibited increased permeability, both under basal and inflammatory conditions, which was associated with disrupted cell-surface localization of the adherens junction protein, vascular endothelial (VE)-cadherin. Protein abundance of VE-cadherin was increased with age, while levels of the adapter protein, -catenin, and the tight junction protein, claudin-5, were decreased. Measures of inflammation, including cytokine expression and cell surface abundance of adhesion molecules, did not differ with age. Augmented presence of actin stress fibers was observed in aged PMVEC. We conclude that aging predisposes PMVEC to elevated injury, due to inherent deficiencies in cell-cell junctions and barrier function, potentially mediated through altered actin cytoskeleton organization.
Insights
Aging impairs pulmonary microvascular endothelial cell (PMVEC) barrier function by disrupting cell-cell junctions. This age-related dysfunction increases lung injury susceptibility, highlighting the need for targeted interventions.
Area of Science:
- Pulmonary vascular research
- Cellular biology
- Aging research
Background:
- Pulmonary microvascular endothelial cell (PMVEC) intercellular junctions are vital for lung barrier integrity.
- Aging exacerbates pulmonary microvascular permeability, suggesting age-related junctional dysfunction.
- Previous studies indicated aging worsens lung injury, prompting this investigation into PMVEC barrier integrity.
Purpose of the Study:
- To investigate the impact of aging on pulmonary microvascular endothelial cell (PMVEC) barrier function and cell-cell junction integrity.
- To determine if aging alters the proteome, inflammatory markers, or actin cytoskeleton in PMVECs.
- To test the hypothesis that aging leads to increased PMVEC barrier dysfunction via impaired cell-cell junctions.
Main Methods:
- Isolated and cultured pulmonary microvascular endothelial cells (PMVECs) from young and aged mice in vitro.
- Assessed barrier function, junctional integrity, proteome alterations, inflammation markers, and actin cytoskeleton organization.
- Stimulated PMVECs with inflammatory cytokines to model injurious conditions.
Main Results:
- Aged PMVECs exhibited increased permeability under basal and inflammatory conditions.
- Disrupted cell-surface localization of vascular endothelial (VE)-cadherin was observed in aged PMVECs.
- VE-cadherin protein abundance increased with age, while -catenin and claudin-5 levels decreased; actin stress fibers were augmented.
Conclusions:
- Aging leads to inherent deficiencies in pulmonary microvascular endothelial cell (PMVEC) junctions and barrier function.
- Increased susceptibility to lung injury in aged individuals may be mediated by impaired cell-cell junctions and altered actin cytoskeleton.
- These findings underscore the role of aging in compromising pulmonary endothelial barrier homeostasis.
