Angiotensin II interferes with leukemia inhibitory factor-induced STAT3 activation in cardiac myocytes

Recently, we reported that leukemia inhibitory factor (LIP), a member of th e interleukin (IL)-6 cytokine family, transduced hypertrophic and cytoprote ctive signals via Januas Kinase-signal transducer and activator of transcri ption (JAK-STAT) pathway in cardiac myocytes. Angiotensin II (AII) is also known to activate STATs and reported to induced apoptosis in adult rat vent ricular myocytes. In the present study, we investigated potential interacti ons between gp130 dependent and AZT signaling pathways, by examining AII re gulation of LIF-induced anti-apoptotic effect and STAT3 activation in cardi ac myocytes. Although LIF attenuated the DNA fragmentation induced by serum depletion, AII aug augmented the DNA fragmentation in cultured neonatal ra t cardiac myocytes, Furthermore, LIF-mediated cytoprotective effect was inh ibited by AII pretreatment. LIF rapidly and transiently tyrosine phosphoryl ated STAT3 in cardiac myocytes which was not observed by AII. AII pretreatm ent inhibited LIF-induced phosphorylation of STAT3 in a dose dependent mann er. This inhibitory effect of AII on STAT3 activation was blocked by the AI I type I (AT1) receptor antagonist CV11974. These results demonstrate that negative crosstalk between gp130 and ATI receptor dependent signaling exist s in cardiac myocytes, This crosstalk may contribute to the modulation of p athophysiological process in myocardial disease. (C) 1998 Academic Press.