Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in Zebrafish

Area of Science:

• Vascular Biology
• Endothelial Cell Biology
• Zebrafish Models

Background:

• Endothelial cells form a semipermeable barrier regulating vessel function.
• Fatty acid binding proteins (FABPs) bind hydrophobic molecules and are involved in homeostasis and angiogenesis.
• FABP4 is a key mammalian member of the FABP family.

Purpose of the Study:

• To investigate the role of fabp11a, the zebrafish ortholog of FABP4, in brain vascular development and integrity.
• To determine the impact of fabp11a loss-of-function on endothelial barrier function.

Main Methods:

• Zebrafish model system utilized for genetic studies.
• Gene knockout and morpholino-mediated knockdown of fabp11a.
• Assessment of brain hemorrhage and vascular permeability.
• Pharmacological inhibition of cyclooxygenase (COX) and lipoxygenase (LOX) pathways.

Main Results:

• fabp11a is highly expressed in developing zebrafish brain vasculature.
• Loss of fabp11a leads to significant brain hemorrhage and increased vascular permeability.
• Morpholino knockdown of fabp11a recapitulates the observed vascular defects.
• Inhibition of COX and LOX partially rescues the vascular integrity defects.

Conclusions:

• fabp11a is essential for maintaining zebrafish brain vascular integrity.
• FABP4/fabp11a function in vascular health may involve fatty acid metabolism pathways (COX/LOX).
• This study highlights a novel role for FABP4 orthologs in vascular barrier function.