Inhibiting STAT5 significantly attenuated Ang II-induced cardiac dysfunction and inflammation.

ABSTRACT

Cardiac hypertrophy is a compensatory response to chronic pressure overload. Excessive angiotensin II is an important inducer of cardiac hypertrophy. Signal transducers and activators of transcription 5(STAT5), a member of STATs family which can mediate the transcription of interferon (IFN) genes and immune response has recently been reported to have a close link with non-tumor diseases. However, much remains unknown about how STAT5 might be involved in the progression of hypertrophy. Herein, STAT5-IN-1, a STAT5 inhibitor, was orally administered to Ang II-induced mice. Ang II-stimulated H9c2s cells were used as cell models for the in vitro experiment. Efforts were made to investigate the effects of STAT5-IN-1 in Ang II-induced mice, along with potential mechanism that might account for these effects, which involved treatment with STAT5 inhibitor and the use of siRNA-induced gene silencing. The findings demonstrated that STAT5 inhibitor resulted in a substantial decrease in cardiac hypertrophy in Ang II-induced mice and that this effect is mediated by decreasing inflammation, thus identifying one mechanism of Ang II-induced STAT5 activation. Based on these findings, it can be argued that targeting STAT5 mighted be considered as a potential therapeutic strategy for reducing hypertrophy.