Doxycycline attenuates burn-induced microvascular hyperpermeability.

Area of Science:

• Biomedical Science
• Physiology
• Pharmacology

Background:

• Severe burns cause systemic microvascular hyperpermeability, leading to shock and cardiovascular collapse.
• Endothelial cell adherens junction damage is critical in burn pathophysiology.
• Matrix metalloproteinases (MMPs) are implicated in this process.

Purpose of the Study:

• To investigate if doxycycline, an MMP inhibitor, can reduce burn-induced adherens junction damage and microvascular hyperpermeability.
• To elucidate the role of MMP-9 in burn-induced vascular changes.

Main Methods:

• Male Sprague-Dawley rats received a 30% total body surface area burn.
• Intravital microscopy assessed albumin flux in mesenteric venules.
• In vitro studies used rat lung microvascular endothelial cells treated with burn serum, with or without doxycycline or an MMP-9 inhibitor.

Main Results:

• Burn serum significantly increased endothelial monolayer permeability and adherens junction disruption, which was reversed by doxycycline and an MMP-9 inhibitor.
• Intravital microscopy confirmed doxycycline attenuated burn-induced microvascular hyperpermeability.
• MMP-9 levels and activity were elevated post-burn.

Conclusions:

• Burns induce microvascular hyperpermeability through MMP-9-mediated endothelial adherens junction disruption.
• Doxycycline effectively attenuates these burn-induced vascular changes.
• Targeting MMP-9 offers a potential therapeutic strategy for burn management.