title: Endothelin-1 induced proinflammatory markers in the myocardium and leukocytes of guinea-pigs: role of glycoprotein IIB/IIIA receptors.
abstract: OBJECTIVE
  To assess whether endothelin-1 (ET-1) induces the in vivo expression of inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor, in the myocardium and circulating leukocytes of guinea-pigs. The involvement of platelets was also analyzed.
  
  
  METHODS
  ET-1 (0.013 microg/min) was infused to male guinea-pigs for 45 min in the presence and absence of tirofiban, a nonpeptidic blocker of the glycoprotein IIb/IIIa receptor (GPIIb/IIIa). Tissue factor and COX-2 expression were determined by Western blot.
  
  
  RESULTS
  No changes in mean arterial pressure and heart rate were detected. ET-1-infused guinea-pigs showed a marked increase in the number of platelets expressing activated GPIIb/IIIa receptors (0.8+/-0.03% vs. 6.5+/-0.2%; P<0.05). Tirofiban (10 microg/Kg bw/min) blunted ex vivo platelet aggregation in response to ADP, although only partially reduced COX-2 and tissue factor expression in both the myocardium and leukocytes of ET-1-infused guinea-pigs. The myocardium of platelet-depleted guinea-pigs also showed a reduced COX-2 expression after ET-1 infusion (57+/-3% reduction; P<0.05). In vitro studies demonstrated that platelets (10(7) and 10(9) platelets/well) enhanced ET-1 (10(-7) mol/l)-induced COX-2 expression in heart slices.
  
  
  CONCLUSIONS
  ET-1 stimulated in vivo the expression of the pro-inflammatory proteins COX-2 and tissue factor in the myocardium and in leukocytes by a mechanism GPIIb/IIIa platelet receptors.
authors.affiliation: Cardiovascular Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos, 2, Madrid, 28040 Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Molero
authors.forename: Jeronimo
authors.initials: J
authors.lastname: Farré
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Mendez
authors.forename: Petra
authors.initials: P
authors.lastname: Jiménez Mateos-Caceres
authors.forename: Carolina
authors.initials: C
authors.lastname: Carrasco Martín
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Millás
authors.forename: Felipe
authors.initials: F
authors.lastname: Navarro
authors.forename: Manuel
authors.initials: M
authors.lastname: Córdoba
authors.forename: Santos
authors.initials: S
authors.lastname: Casado
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Farré
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D019332:Endothelin-1 / Q000494:pharmacology*; D006168:Guinea Pigs; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism; D013268:Stimulation, Chemical; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D007527:Isoenzymes; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D013925:Thromboplastin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000077466:Tirofiban