Induction of angiotensin-converting enzyme by oncostatin M in human endothelial cells

Objective: To examine the role of oncostatin M (OSM) in the regulation of angiotensin converting enzyme (ACE) in endothelial cells. Methods: Cultured endothelial cells were incubated with OSM (25-200 pM) for 24 h, Incubations were performed without or with the tyrosine kinase inhibitor, herbimycin (87 nM), or the selective MAP kinase kinase inhibitor, PD98059 (50 mu M), ACE amount in intact endothelial cells was measured by an inhibitor binding assay and ACE mRNA levels by RNase protection assay. Results: OSM caused a dose dependent increase in ACE amount and increased the expression of ACE mRNA, The stimulatory effect of OSM was inhibited by pretreatments with herbimycin or PD98059, Conclusions: OSM induced ACE in cultured HUVECs. Tyrosine kinase and MAPK activation were probably involved in ACE induction. Local induction of ACE by OSM in the vascular wall may be a consequence of inflammatory processes leading to locally increased production of angiotensin II and breakdown of bradykinin, (C) 2000 Academic Press.