Endothelin-1 induced proinflammatory markers in the myocardium and leukocytes of guinea-pigs: Role of glycoprotein IIB/IIIA receptors
- 作者：Molero ; Laura ; Farré ; Jeronimo ; Garcí ; a-Mendez ; Antonio ; Jimé ; nez Mateos-Caceres ; Petra ; et. al.
- 关键词：Endothelial factors ; Endothelins ; Infection/inflammation ; Leukocytes ; Myocytes ; Platelets
- 刊名：Cardiovascular Research
- 出版年：2003
- 期刊代码：48_00086363
- 类别：med
- 出版时间：January, 2003
- 卷：57
- 期：1
- 页码：109-118
- 文件大小：777 K
摘要
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.