title: Angiotensin blockade inhibits SIF DNA binding activities via STAT3 after myocardial infarction.
abstract: The in vivo activation of transcription factors, which is important for cell regulation by gene expression, has not been well examined in myocardial infarcted heart. The purpose of this study was to determine whether myocardial signal transducer and activator of transcription (STAT) pathway is activated as sis-inducing factor (SIF) in infarcted heart, and to assess the angiotensin blockade on SIF activity in ischemic and non-ischemic myocardium of rat. Myocardial infarction was made by ligation of the coronary artery in Wistar rats. In electrophoretic mobility shift assay, myocardial SIF DNA binding activities gradually increased and reached to peak at 1 week in infarcted and non-infarcted regions after myocardial infarction. Imidapril and candesartan cilexitil significantly prevented the increase in SIF DNA binding activity in infarcted and non-infarcted regions. This increased SIF DNA complex was supershifted by specific anti-STAT3 antibody, indicating that increased SIF complex at least contained activated STAT3 proteins in myocardial infarcted heart. Furthermore, immunoprecipitation-Western blot analysis revealed that STAT3 of infarcted and non-infarcted regions were tyrosine-phosphorylated at 1 week after myocardial infarction. Imidapril and candesartan cilexitil prevented the increase in phosphorylated STAT3. Thus, the transcriptional activation of STAT3 through AT1 receptor may be partially involved in cardiac remodeling after myocardial infarction.
authors.affiliation: First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Omura
authors.forename: M
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Iwao
authors.forename: H
authors.initials: H
authors.lastname: Yamagishi
authors.forename: I
authors.initials: I
authors.lastname: Toda
authors.forename: M
authors.initials: M
authors.lastname: Teragaki
authors.forename: K
authors.initials: K
authors.lastname: Akioka
authors.forename: J
authors.initials: J
authors.lastname: Yoshikawa
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006352:Heart Ventricles; D006439:Hemodynamics; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004268:DNA-Binding Proteins; D007093:Imidazoles; D048289:Imidazolidines; D050796:STAT3 Transcription Factor; D016329:Sp1 Transcription Factor; C494088:Stat3 protein, rat; D013777:Tetrazoles; D015534:Trans-Activators; D014443:Tyrosine; C065166:imidapril; C081643:candesartan