All-trans retinoic acid modulates the balance of ADAMTS13 and VWF in human microvascular endothelial cells.

ABSTRACT

PURPOSE: To better understand the antithrombotic property of All-trans retinoic acid (ATRA), we investigated whether ATRA may affect the balance between ADAMTS13 and von Willebrand factor (VWF) in human microvascular endothelial cell. METHODS: Compared to tumor necrosis factor-alpha (TNF-α), we observed the effects of ATRA on the expression of ADAMTS13 and VWF. ADAMTS13mRNA in human microvascular endothelial cell (HMEC-1 cell line) were detected by real-time polymerase chain reaction amplification (RT-PCR). The levels of ADAMTS13 and VWF antigen were detected by western blot or enzyme-linked immunosorbent assay (ELISA), and the proteolytic activity of ADAMTS13 was also determined by using GST-VWF73-His peptide as a specific substrate. RESULTS: ATRA significantly upregulated the expression of ADAMTS13mRNA in HMEC-1, while TNF-α inhibited ADAMTS13mRNA expression. ATRA could reverse the inhibition expression of ADAMTS13 by TNF-α. The results were confirmed from the levels of ADAMTS13 protein and its activity, while ATRA had no significant affection on triggering release of VWF. CONCLUSIONS: This study provides the evidence that ATRA modulates the balance of ADAMTS13 and VWF in human microvascular endothelial cell, which might be a very relevant compartment for the antithrombotic property of ATRA.