Abstract 218: Orphan Nuclear Receptor Nur77 is a Novel Negative Regulator of ET-1 Expression in Vascular Endothelial Cells

ObjectiveEndothelin-1 (ET-1), a vasoactive peptide mainly produced by vascular endothelial cells, plays an important role in the regulation of vascular tone and the development of cardiovascular diseases. The objective of the present study is to identify the novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs), and to determine the molecular mechanism involved. Method and Resultsby using quantitative real-time PCR (qRT-PCR) and Enzyme-linked immunosorbent assay (ELISA), we showed that either ectopic expression of Nur77 or pharmacological activation of Nur77 by 6-mercaptopurine (6-MP) substantially inhibited the ET-1 expression, under both basal and thrombin stimulated conditions, in human umbilical vein endothelial cells (HUVECs). Furthermore, knockdown of Nur77 enhances both basal and thrombin induced ET-1 expression, suggesting that Nur77 is a negative regulator of the ET-1 expression in vascular ECs. Inhibition of ET-1 expression by Nur77 mainly occurs at...