Hypobaric hypoxia down-regulated junctional protein complex: Implications to vascular leakage

Area of Science:

• Physiology
• Cell Biology
• Pathophysiology

Background:

• Acute mountain sickness (AMS) is linked to capillary hyper-permeability and vasogenic edema.
• The precise mechanisms driving AMS-induced vascular changes remain incompletely understood.
• No prior in vitro studies have investigated the cellular basis of AMS.

Purpose of the Study:

• To investigate whether continuous hypobaric hypoxia (CHH) alters junctional protein complex expression in vascular endothelial cells.
• To determine if CHH induces hyper-permeability in endothelial cell monolayers.
• To explore the cellular mechanisms underlying vascular dysfunction in AMS.

Main Methods:

• EA.hy926 human endothelial cells were exposed to CHH or normoxia for up to 24 hours.
• Cell death was assessed using flow cytometry (annexin V/propidium iodide).
• Transendothelial electrical resistance (TER) measured monolayer permeability.
• Western blot and immunofluorescence analyzed junctional protein (VE-cadherin, PECAM-1, ZO-1) expression.

Main Results:

• CHH exposure increased endothelial cell death at 24 hours but not at 12 hours.
• TER significantly decreased under CHH from 1 to 24 hours, indicating increased permeability.
• CHH reduced expression of VE-cadherin, PECAM-1, and ZO-1, with increased degradation of ZO-1 at 24 hours.

Conclusions:

• Continuous hypobaric hypoxia (CHH) induces vascular endothelial hyper-permeability.
• CHH disrupts the endothelial junctional protein complex by reducing VE-cadherin, PECAM-1, and ZO-1 expression.
• These findings provide in vitro evidence for the pathophysiology of vascular hyper-permeability in acute mountain sickness (AMS).