Endothelin-1 Expression by Vascular Endothelial Growth Factor in Human Umbilical Vein Endothelial Cells and Aortic Smooth Muscle Cells

Abstract

Objective. This study investigated endothelin-1 (ET-1) production induced by vascular endothelial growth factor (VEGF) in two different vascular wall cell types. Methods. We analyzed the effect of endothelin-converting enzyme-1 (ECE-1) inhibitor and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) on VEGF-induced ET-1 expression using real-time polymerase chain reaction and enzyme-linked immunosorbent assay in human umbilical vein endothelial cells and aortic smooth muscle cells. Results. In human umbilical vein endothelial cells, both phosphoramidon, an inhibitor of ECE-1, and TIMP-2 decreased VEGF-induced ET-1 production. In aortic smooth muscle cells, TIMP-2 suppressed VEGF-induced ET-1 production, but phosphoramidon did not influence ET-1 concentration in culture. Conclusion. VEGF-induced ET-1 production may be MMP-2- or ECE-1-dependant in endothelial cells; however, in smooth muscle cells, ET-1 expression appears to be induced by MMP-2 only.