Abstract
The monolayer of endothelial cells (ECs) lining the intima of all blood vessel wall forms a semipermeable barrier that regulates tissue-fluid homeostasis, transport of nutrients, and migration of blood cells across the barrier. A number of signaling pathways and molecules mediate endothelial permeability, which plays important roles in a variety of the physiological and pathological conditions. Fatty acid binding proteins (FABPs) are able to bind various hydrophobic molecules, such as long-chain fatty acids, prostaglandins and eicosanoids. FABP4, a member of the family of FABPs, plays an important role in maintenance of glucose and lipid homeostasis as well as angiogenesis. In the present study, we found that fabp11a, the ortholog of mammalian FABP4, was highly expressed in developing brain vessels of zebrafish. Knockout of fabp11a gene caused hemorrhage in zebrafish brain. Morpholino mediated fabp11a gene knockdown phenocopied the hemorrhage in mutants. Furthermore, we demonstrated permeability of brain vessels in fabp11a mutant is significantly higher than that of control. In addition, COX and LOX inhibition partially rescued the brain vessel integrity defects caused by fabp11a loss-of-function, suggesting the integrity defect was relevant to the Fatty Acid function.
Highlights
The vascular system of vertebrates composed of a well-organized and hierarchical network of blood vessels, including arteries, veins, and capillaries
We demonstrated that the hemorrhage phenotype could be rescued by co-injection of fabp11a mRNA together with fabp11a morpholino oligonucleotide (MO) (Figure S1E)
These results suggest that fabp11a regulates brain vessel integrity in zebrafish
Summary
The vascular system of vertebrates composed of a well-organized and hierarchical network of blood vessels, including arteries, veins, and capillaries This network overspreads throughout every tissue and organ of the body and is adapt to the physiological function in local microenvironment (Risau, 1997; Carmeliet and Tessier-Lavigne, 2005; Larrivee et al, 2009). Vasculogenesis is a de novo formation of the blood vessels, whereas angiogenesis is the outgrowth of endothelial cells (ECs) to form new branches from a pre-existing vasculature (Risau and Flamme, 1995; Risau, 1997). Recent studies in mice have shown that endothelial FABP4 are involved in some angiogenesis-related processes, such as EC survival, migration, and angiogenic sprouting (Elmasri et al, 2012). Current study provides new insight into the role of fatty acid binding protein in blood vessel
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