We studied the effects of factors associated with vascular injury on the production of endothelin-1 (ET-1) in cultured porcine aortic endothelial cells. ET-1 mRNA expression and peptide production in endothelial cells were increased by thrombin, transforming growth factor β1 (TGFβ1), interleukin-1 (IL-1) and tumor necrotizing factor α (TNFα). The analysis of the enhancer/promoter region of the human ET-1 gene showed that the ET-1 gene transcription is regulated in a cell-specific manner and is activated by thrombin, TGFβ1 and IL-1. These results suggest that the production of ET-1 in endothelial cells is regulated by factors associated with platelet aggregation, macrophage infiltration and the formation of atherosclerotic lesions.

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