Endothelial Cell Calcium Influx Mediates Trauma-induced Endothelial Permeability.

Area of Science:

• Trauma research
• Endothelial biology
• Calcium signaling

Background:

• Endothelial permeability is a key factor in post-trauma organ dysfunction.
• The precise mechanisms driving this increased permeability remain incompletely understood.
• Emerging evidence points to a potential role for intracellular calcium (Ca 2+ ) signaling pathways.

Purpose of the Study:

• To determine if plasma from injured patients induces endothelial Ca 2+ influx.
• To investigate Ca 2+ influx as a mechanism for trauma-induced endothelial permeability.
• To explore the role of the TRPV4 channel in this process.

Main Methods:

• Treatment of endothelial cells with ex vivo plasma from trauma patients (categorized by injury/shock severity).
• Experimental manipulation of extracellular Ca 2+ levels and intracellular Ca 2+ stores.
• Pharmacological inhibition of the transient receptor potential vanilloid 4 (TRPV4) channel.
• Assessment of cytosolic Ca 2+ levels, endothelial permeability, and cytoskeletal changes using microscopy and impedance sensing.

Main Results:

• Plasma from severely injured/shocked patients induced significantly greater cytosolic Ca 2+ increase compared to less severely injured patients.
• Endothelial Ca 2+ influx and subsequent permeability were dependent on extracellular Ca 2+.
• Inhibition of TRPV4 channels reduced trauma plasma-induced Ca 2+ influx and endothelial permeability.

Conclusions:

• A novel mechanism of post-trauma endotheliopathy involves Ca 2+ influx through TRPV4 channels.
• TRPV4 inhibition demonstrates potential in mitigating trauma-induced endothelial permeability.
• Findings suggest a mechanistic link between endothelial Ca 2+ influx and trauma-induced hypocalcemia, paving the way for Ca 2+ targeted therapies.