Sphingosine-1-phosphate Maintains Normal Vascular Permeability by Preserving Endothelial Surface Glycocalyx in Intact Microvessels

ObjectiveS1P was found to protect the ESG by inhibiting MMP activity-dependent shedding of ESG in cultured endothelial cell studies. We aimed to further test that S1P contributes to the maintenance of normal vascular permeability by protecting the ESG in intact microvessels. MethodsWe quantified the ESG in post-capillary venules of rat mesentery and measured the vascular permeability to albumin in the presence and absence of 1M S1P. We also measured permeability to albumin in the presence of MMP inhibitors and compared the measured permeability with those predicted by a transport model for the inter-endothelial cleft. ResultsWe found that in the absence of S1P, the fluorescence intensity of the FITC-anti-HS-labeled ESG was similar to 10% of that in the presence of S1P, whereas the measured permeability to albumin was similar to 6.5-fold of that in the presence of S1P. Similar results wereobserved with MMP inhibition. The predictions by the mathematical model further confirmed that S1P maintains microvascular permeability by preserving ESG. ConclusionsOur results show that S1P contributes to the maintenance of normal vascular permeability by protecting the ESG in intact microvessels, consistent with parallel observation in cultured endothelial monolayers.