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

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 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. 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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Molero L,Farré J,García-Mendez A,Jiménez Mateos-Caceres P,Carrasco Martín C,Millás I,Navarro F,Córdoba M,Casado S,López-Farré A

doi

10.1016/s0008-6363(02)00657-0

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

109-18

issue

1

eissn

0008-6363

issn

1755-3245

pii

S0008636302006570

journal_volume

57

pub_type

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