title: Sphingosine-1-phosphate Maintains Normal Vascular Permeability by Preserving Endothelial Surface Glycocalyx in Intact Microvessels.
abstract: 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.
  
  
  
  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 μM 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York City, New York, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York City, New York, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York City, New York, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York City, New York, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Tarbell
authors.affiliation: Department of Physiology and Membrane Biology, School of Medicine, University of California at Davis, Davis, California, USA.
authors.forename: Fitz-Roy E
authors.initials: FR
authors.lastname: Curry
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York City, New York, USA.
authors.forename: Bingmei M
authors.initials: BM
authors.lastname: Fu
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D019276:Glycocalyx / Q000502:physiology*; D008246:Lysophospholipids / Q000502:physiology*; D008643:Mesentery / Q000098:blood supply; D055806:Microvessels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: heparan sulfate; in situ immunostaining; matrix metalloproteinase; rat mesentery; transport model for the inter-endothelial cleft