title: Effect of ischemia reperfusion injury and epoxyeicosatrienoic acids on caveolin expression in mouse myocardium.
abstract: BACKGROUND
  Caveolins (Cav) are structural proteins that insert into the plasma membrane to form caveolae that can bind molecules important in cardiac signal transduction and function. Cytochrome P450 epoxygenases can metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) which have known cardioprotective effects. Subsequent metabolism of EETs by soluble epoxide hydrolase reduces the protective effect.
  
  
  OBJECTIVE
  (1) To assess the effect of ischemia-reperfusion injury on expression and subcellular localization of caveolins. (2) To study the effect of EETs on caveolins.
  
  
  METHODS
  Hearts from soluble epoxide hydrolase null (KO) and littermate control (WT) mice were perfused in Langendorff mode and subjected to 20 minutes ischemia followed by 40 minutes reperfusion. Immunohistochemistry, immunoblot, and electron microscopy were performed to study localization of caveolins and changes in ultrastructure.
  
  
  RESULTS
  In WT heart, Cav-1 and Cav-3 were present in cardiomyocyte and capillary endothelial cell at baseline. After ischemia, Cav-1 but not Cav-3, disappeared from cardiomyocyte; moreover, caveolae were absent and mitochondrial cristae were damaged. Improved postischemic functional recovery observed in KO or WT hearts treated with 11,12-EET corresponded to higher Cav-1 expression and maintained caveolae structure. In addition, KO mice preserved the Cav-1 signaling after ischemia that lost in WT mice.
  
  
  CONCLUSIONS
  Taken together, our data suggest that ischemia-reperfusion injury causes loss of Cav-1 and caveolins, and EETs-mediated cardioprotection involves preservation of Cav-1.
authors: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors: Ketul R
authors: KR
authors: Chaudhary
authors: Woo Jung
authors: WJ
authors: Cho
authors: Fenghua
authors: F
authors: Yang
authors: Victor
authors: V
authors: Samokhvalov
authors: Haitham E
authors: HE
authors: El-Sikhry
authors: Edwin E
authors: EE
authors: Daniel
authors: John M
authors: JM
authors: Seubert
mesh_terms: D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D021941:Caveolae / Q000378:metabolism* / Q000648:ultrastructure; D051242:Caveolin 1 / Q000378:metabolism*; D051244:Caveolin 3 / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000378:metabolism / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010477:Perfusion; D015398:Signal Transduction
chemical_list: C495541:Cav1 protein, mouse; C495548:Cav3 protein, mouse; D051242:Caveolin 1; D051244:Caveolin 3; D015777:Eicosanoids; D004851:Epoxide Hydrolases; C518648:Ephx2 protein, mouse