STAT3 and cardiac remodeling.
Multiple in vitro and in vivo studies showed that the signal transducer and activator of transcription 3 (STAT3) protein is involved in cardiomyocyte protection and hypertrophy and via paracrine pathways impacts on the non-myocyte compartment, i.e., the vasculature and the extracellular matrix. In this regard, STAT3 interacts with a broad range of cellular and molecular mechanisms that direct remodeling processes in cardiac physiology (exercise, pregnancy) and pathophysiology (pressure overload, ischemia/reperfusion, myocardial infarction, and cardiotoxic agents). STAT3 is constitutively activated by a multitude of factors including cytokines, growth factors, neurohormones, mechanical load, and ischemia. It acts as a signaling molecule, a transcription factor and according to latest observations as a mitochondrial protein involved in energy production. In this review, we provide an overview on STAT3 signaling and summarize the current understanding of the role of STAT3 for different aspects of cardiac remodeling obtained from numerous experimental and clinical studies. Finally, we highlight and critically discuss STAT3 signaling as a possible target for future therapeutic approaches in the setting of cardiac remodeling.
Haghikia
Arash
A
Department of Cardiology and Angiology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Stapel
Britta
B
Hoch
Melanie
M
Hilfiker-Kleiner
Denise
D
D000375:Aging; D000804:Angiotensin II; D002311:Cardiomyopathy, Dilated / Q000473:pathology*; D005109:Extracellular Matrix; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D020257:Ventricular Remodeling
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000804:Angiotensin II
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