Angiotensin blockade inhibits SIF DNA binding activities via STAT3 after myocardial infarction

The in vivo activation of transcription factors, which is important for cel l regulation by gene expression, has not been well examined in myocardial i nfarcted heart. The purpose of this study was to determine whether myocardi al signal transducer and activator of transcription (STAT) pathway is activ ated as sis-inducing factor (SIF) in infarcted heart, and to assess the ang iotensin blockade on SIF activity in ischemic and non-ischemic myocardium o f rat. Myocardial infarction was made by ligation of the coronary artery in Wistar rats. In electrophoretic mobility shift assay, myocardial SIF DNA b inding activities gradually increased and reached to peak at 1 week in infa rcted and non-infarcted regions after myocardial infarction. Imidapril and candesartan cilexitil significantly prevented the increase in SIF UNA bindi ng activity in infarcted and non-infarcted regions. This increased SIF DNA complex was supershifted bg specific anti-STAT3 antibody, indicating that i ncreased SIF complex at least contained activated STAT3 proteins in myocard ial infarcted heart. Furthermore, immunoprecipitation-Western blot analysis revealed that STAT3 of infarcted and non-infarcted regions were tyrosine-p hosphorylated at 1 week after myocardial infarction, Imidapril and candesar tan cilexitil prevented the increase in phosphorylated STAT3. Thus, the tra nscriptional activation of STAT3 through AT1 receptor may be partially invo lved in cardiac remodeling after myocardial infarction. (C) 2000 Academic P ress.