Abstract
SummaryLysophosphatidic acid (LPA) is a potential regulator of vascular formation derived from blood. In this study, we utilized zebrafish as a model organism to monitor the blood vessel formation in detail. Zebrafish mutant of ATX, an LPA-producing enzyme, had a defect in the caudal vein plexus (CVP). Pharmacological inhibition of ATX resulted in a fusion of the delicate vessels in the CVP to form large sac-like vessels. Mutant embryos of LPA6 receptor and downstream Gα13 showed the same phenotype. Administration of OMPT, a stable LPA-analog, induced rapid CVP constriction, which was attenuated significantly in the LPA6 mutant. We also found that blood flow-induced CVP formation was dependent on ATX. The present study demonstrated that the ATX-LPA6 axis acts cooperatively with blood flow and contributes to the formation and maintenance of the CVP by generating contractive force in endothelial cells.
Highlights
Vascular endothelial growth factor (VEGF, mainly VEGF-A) has received the most attention as the central molecule responsible for angiogenesis (Apte et al, 2019)
Pharmacological inhibition of ATX resulted in a fusion of the delicate vessels in the caudal vein plexus (CVP) to form large sac-like vessels
We found that blood flow-induced CVP formation was dependent on ATX
Summary
Vascular endothelial growth factor (VEGF, mainly VEGF-A) has received the most attention as the central molecule responsible for angiogenesis (Apte et al, 2019). After initial vessel structures have been established, the vessels are filled with blood and undergo further vascular remodeling, including stabilization, diameter adjustment, and regression, resulting in a proper vascular network (Jones et al, 2006; Jones, 2011; Tanaka and Laurindo, 2017). Blood-derived factors may have some roles in this process. S1P is present in the bloodstream at a high concentration ($1 mM). It contributes to vascular stabilization by strengthening endothelial cell-cell adhesion via several G protein-coupled receptors (GPCR) specific to S1P (Yanagida and Hla, 2017). LPA has been implicated in embryonic blood vessel formation because knockout mice of an enzyme involved in LPA synthesis (autotaxin (ATX)) and LPA receptors (LPA4 and LPA6) showed similar vascular defects in embryos around E10.5 (Tanaka et al, 2006; van Meeteren et al, 2006; Koike et al, 2009; Kano et al, 2019; Yasuda et al, 2019)
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