TITLE

Endothelin-1 induced proinflammatory markers in the myocardium and leukocytes of guinea-pigs: Role of glycoprotein IIB/IIIA receptors

AUTHOR(S)
Molero, Laura; Farré, Jeronimo; Garcıa-Mendez, Antonio; Jiménez Mateos-Caceres, Petra; Carrasco Martın, Carolina; Millás, Inmaculada; Navarro, Felipe; Córdoba, Manuel; Casado, Santos; López-Farré, Antonio
PUB. DATE
January 2003
SOURCE
Cardiovascular Research;Jan2003, Vol. 57 Issue 1, p109
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Aim: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 μg/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 μg/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 (107 and 109 platelets/well) enhanced ET-1 (10−7 mol/l)-induced COX-2 expression in heart slices. Conclusion: 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.
ACCESSION #
8724682

 

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