title: Understanding STAT3 signaling in cardiac ischemia.
abstract: Cardiovascular disease is the leading cause of death worldwide. It remains one of the greatest challenges to global health and will continue to dominate mortality trends in the future. Acute myocardial infarction results in 7.4 million deaths globally per annum. Current management strategies are centered on restoration of coronary blood flow via percutaneous coronary intervention, coronary artery bypass grafting and administration of anti-platelet agents. Such myocardial reperfusion accounts for 40-50 % of the final infarct size in most cases. Signaling transducer and activator of transcription 3 (STAT3) has been shown to have cardioprotective effects via canonical and non-canonical activation and modulation of mitochondrial and transcriptional responses. A significant body of in vitro and in vivo evidence suggests that activation of the STAT3 signal transduction pathway results in a cardio protective response to ischemia and attempts have been made to modulate this with therapeutic effect. Not only is STAT3 important for cardiomyocyte function, but it also modulates the cardiac microenvironment and communicates with cardiac fibroblasts. To this end, we here review the current evidence supporting the manipulation of STAT3 for therapeutic benefit in cardiac ischemia and identify areas for future research.
authors.affiliation: The Mater Private Hospital, Eccles St, Dublin 7, Ireland. kaosulli@tcd.ie.
authors.forename: K E
authors.initials: KE
authors.lastname: O'Sullivan
authors.affiliation: The Mater Private Hospital, Eccles St, Dublin 7, Ireland.
authors.forename: E P
authors.initials: EP
authors.lastname: Breen
authors.affiliation: School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.|Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.|UCD-Mater Clinical Research Centre, Catherine McCauley Centre, Nelson St, Dublin 7, Ireland.
authors.forename: H C
authors.initials: HC
authors.lastname: Gallagher
authors.affiliation: The Mater Private Hospital, Eccles St, Dublin 7, Ireland.|School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.|Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.|UCD-Mater Clinical Research Centre, Catherine McCauley Centre, Nelson St, Dublin 7, Ireland.|Outcomes Research Consortium, Cleveland Clinic, Ohio, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Buggy
authors.affiliation: The Mater Private Hospital, Eccles St, Dublin 7, Ireland.
authors.forename: J P
authors.initials: JP
authors.lastname: Hurley
mesh_terms: D000818:Animals; D006801:Humans; D017202:Myocardial Ischemia; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D050796:STAT3 Transcription Factor
keywords: Cardiomyocyte; Fibroblast; HIF-1α; Myocardial ischemia; STAT3