Background
The specific role of lysophosphatidic acid 2 (LPA2) in deep vein thrombosis (DVT) remains unclear.
Conclusion
These data provide a novel mechanism of endothelial barrier protection of LPA2 in DVT.
Methods
An inferior vena cava annulus retraction model of DVT was established in wild-type (WT) and global LPA2 knockout (Lpar2 -/- ) mice. We examined the incidence of DVT, wet weight of thrombus, length of thrombus, assessed endothelial permeability through Evans blue dye assay in vivo, cell viability, and endothelial cell (EC) permeability of mouse inferior vena cava ECs in vitro. Proteomics, histopathology, immunohistochemistry, and western blotting were employed to investigate the role of LPA2 in DVT.
Results
Lpar2 deficiency increased vascular endothelial permeability and promoted the progression of DVT. Histological examination revealed aggravated inflammation in the thrombus of Lpar2 -/- DVT mice. In vitro, Lpar2 -/- resulted in increased permeability of ECs. Proteomic results indicated that DVT after Lpar2 -/- may be related to tight junction (TJ) protein. LPA2 agonist, 2-[4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid, significantly reduced vascular endothelial permeability as well as increased expression of the vascular endothelial TJ protein zonula occludens-1.