title: Epigallocatechin gallate inhibits angiotensin II-induced endothelial barrier dysfunction via inhibition of the p38 MAPK/HSP27 pathway.
abstract: OBJECTIVE
  To investigate the effect of epigallocatechin gallate (EGCG) on angiotensin II (Ang II)-induced stress fiber formation and hyperpermeability in endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were treated with Ang II in the absence or presence of EGCG or mitogen-activated protein kinases (MAPKs) inhibitors. The resulting stress fibers were stained with rhodamine-phalloidin and examined using confocal microscopy. The permeability of the endothelium was tested with fluorescein-isothiocyanate labeled bovine serum albumin (FITC-BSA), and the phosphorylation levels of several proteins were determined using Western blot analysis.
  
  
  RESULTS
  Ang II (1-100 nmol/L) treatment markedly provoked stress fiber formation and hyperpermeability in HUVECs in a time- and dose-dependent manner. These effects were abolished by pretreatment with the p38 MAPK inhibitor SB203580 10 μmol/L, indicating that the Ang II-induced endothelial barrier dysfunction was via activation of the p38 MAPK/HSP27 pathway. Furthermore, treatment with EGCG (5-25) μmol/L inhibited Ang II-induced activation of the p38 MAPK/HSP27 pathway, thereby reducing endothelial stress fiber formation and hyperpermeability.
  
  
  CONCLUSIONS
  Our data demonstrate that EGCG inhibits Ang II-induced endothelial stress fiber formation and hyperpermeability via inactivation of p38 MAPK/HSP27 pathway, and suggest that EGCG may protect against endothelial barrier dysfunction and injury.
authors.affiliation: Department of Pathology, Capital Medical University, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Cui
authors.initials: C
authors.lastname: Tian
authors.forename: Yong
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yue-hong
authors.initials: YH
authors.lastname: Zheng
authors.forename: Quan
authors.initials: Q
authors.lastname: Fang
authors.forename: Hui-hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D022502:Stress Fibers / Q000648:ultrastructure; D014471:Umbilical Veins / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; D007093:Imidazoles; D011725:Pyridines; D000804:Angiotensin II; D002392:Catechin; C045651:epigallocatechin gallate; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580