ICAM-1 Expression on Cardiac Myocytes and Aortic Endothelial Cells via Their Specific Endothelin Receptor Subtype

Abstract

Endothelin-1 (ET-1) and Endothelin-3 (ET-3) increased the expression of intercellular adhesion molecule-1 (ICAM-1) on rat neonatal cultured cardiac myocytes and rat aortic endothelial cells. ET-1-induced ICAM-1 expression on cardiac myocytes was inhibited by a selective ETAreceptor antagonist, S-0139, but not by a selective ETBreceptor antagonist, BQ788. ET-3-induced ICAM-1 expression on endothelial cells was inhibited by BQ788 but not by S-0139. Protein kinase C (PKC) inhibitor staurosporine inhibited ETs-induced ICAM-1 expression on both cell types. Treatment of the cells with ETs increased neutrophil adhesion, which was inhibited by S-0139 and staurosporine on cardiac myocytes and by BQ788 and staurosporine on endothelial cells. These results suggest that ETs induce neutrophil adhesion to cardiac myocytes and aortic endothelial cells by increasing ICAM-1 expression, which mediate via ETAreceptor on cardiac myocytes and via ETBreceptor on aortic endothelial cells. ICAM-1 expression induced by activation of ETAand ETBreceptors appears to be mediated through the PKC pathway.