title: Amelioration of inflammation and cytotoxicity by dipyridamole in brain endothelial cells.
abstract: BACKGROUND
  Increasing evidence suggests that beyond its antiplatelet properties, dipyridamole may have pleiotropic effects on other cells within the neurovascular elements of the brain. In this experimental cellular study, we asked whether dipyridamole can ameliorate brain endothelial injury after exposure to inflammatory and metabolic insults.
  
  
  METHODS
  Human brain endothelial cells were grown in culture, and exposed to TNFalpha (continuously for 20 h) or subjected to oxygen-glucose deprivation (OGD; 6 h of insult followed by 18 h recovery). Expression of ICAM-1, VCAM-1 and PECAM-1 were measured by immunoblotting. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the conditioned media were quantified via zymography. MTT mitochondrial activity was measured to assess endothelial cell viability.
  
  
  RESULTS
  Exposure of human brain endothelial cells to TNFalpha (12.5-50 ng/ml) induced a clear increase in protein levels of ICAM-1, VCAM-1 and MMP-9. TNFalpha did not alter PECAM-1. Dipyridamole (1-5 muM) significantly attenuated ICAM-1 and MMP-9 levels after this inflammatory insult. No significant effects of dipyridamole were noted for VCAM-1. Six-hour OGD induced moderate endothelial cell death accompanied by a release of MMP-9. Dipyridamole significantly decreased MMP-9 levels and cell death after this metabolic insult.
  
  
  CONCLUSIONS
  These results suggest that dipyridamole may ameliorate brain endothelial injury after inflammation and/or metabolic insults. How these putative cellular mechanisms may relate to clinical outcomes and conditions in stroke patients remains to be elucidated.
authors.affiliation: Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA. sguo@partners.org
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Guo
authors.forename: Monique
authors.initials: M
authors.lastname: Stins
authors.forename: MingMing
authors.initials: M
authors.lastname: Ning
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
mesh_terms: D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D003603:Cytotoxins; D010726:Phosphodiesterase Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004176:Dipyridamole; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9