Stimulation of Tissue-Type Plasminogen Activator Expression by Retinoic Acid in Human Endothelial Cells Requires Retinoic Acid Receptor p2 Induction

We previously showed the involvement of retinoic acid receptor a (RARa) in the induction of tissue-type plasminogen activator (t-PA) synthesis by RA in human umbilical vein endothelial cells (HUVECs). However, the rather slow onset of this induction of t-PA synthesis suggested an indirect role of RARa. Here, we show that the protein synthesis inhibitor, cycloheximide completely blocks the induction of t-PA by RA, which points to the need of an intermediary protein in t-PA stimulation. This intermediary protein is likely to be RARp2 on the basis of the following findings: (1) the induction of RARp by RA exactly precedes that of t-PA; (2) HUVECs