Sphingosine‐1‐phosphate Maintains Normal Vascular Permeability by Preserving Endothelial Surface Glycocalyx in Intact Microvessels. (May 2016)

• Record Type: Journal Article
• Authors: Zhang, Lin; Zeng, Min; Fan, Jie; Tarbell, John M.; Curry, Fitz‐Roy E.; Fu, Bingmei M.
• Is Part Of: Microcirculation. Volume 23:Number 4(2016)
• Page Start: 301
• Page End: 310
• Publication Date: 2016-05
• Subjects: heparan sulfate -- in situ immunostaining -- matrix metalloproteinase -- transport model for the inter‐endothelial cleft -- rat mesentery; Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12278
• Languages: English
• ISSNs: 1073-9688

Abstract

Abstract: Objective: S1P 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. Methods: We quantified the ESG in post‐capillary venules of rat mesentery and measured the vascular permeability to albumin in the presence and absence of 1 μ M 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. Results: We found that in the absence of S1P, the fluorescence intensity of the FITC‐anti–HS‐labeled ESG was ~10% of that in the presence of S1P, whereas the measured permeability to albumin was ~6.5‐fold of that in the presence of S1P. Similar results were observed with MMP inhibition. The predictions by the mathematical model further confirmed that S1P maintains microvascular permeability by preserving ESG. Conclusions: Our 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.