Dabigatran: its protective effect against endothelial cell damage by oxysterol

Area of Science:

• Endothelial biology
• Pharmacology
• Inflammation research

Background:

• Oxysterols like 25-hydroxycholesterol (25-OHC) can compromise endothelial barrier integrity.
• Inflammatory responses in endothelial cells are implicated in various vascular diseases.

Purpose of the Study:

• To investigate the impact of dabigatran on endothelial cell integrity and inflammatory markers when stimulated by 25-OHC.
• To assess dabigatran's potential to counteract 25-OHC-induced endothelial dysfunction.

Main Methods:

• Human Umbilical Vein Endothelial Cells (HUVECs) were treated with 25-OHC, dabigatran, or a combination.
• Endothelial integrity and permeability were measured using the xCELLigence system and paracellular flux assays.
• Gene expression (ICAM-1, VEGF, IL-33, MCP-1, TNF-α), apoptosis, viability, and VE-cadherin expression were analyzed.

Main Results:

• 25-OHC significantly reduced HUVEC integrity and increased pro-inflammatory gene expression.
• Dabigatran treatment restored endothelial integrity disrupted by 25-OHC.
• Dabigatran decreased the expression of inflammatory cytokines (IL-33, TNF-α) and chemokines (MCP-1, ICAM-1) induced by 25-OHC.
• Dabigatran enhanced VE-cadherin expression in 25-OHC-stimulated cells.

Conclusions:

• Dabigatran demonstrates protective effects on endothelial cells against 25-OHC-induced damage.
• Dabigatran stabilizes the endothelial barrier function.
• Dabigatran exhibits anti-inflammatory properties in the context of oxysterol exposure.