STAT3 and cardiac remodeling

Abstract

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.

Resveratrol suppresses the STAT3 signaling pathway and inhibits proliferation of high glucose-exposed HepG2 cells partly through SIRT1

“…STAT3 is activated through phosphorylation of tyrosine 705 in response to various cytokines and growth factors including interferons, epidermal growth factor, interleukin (IL)-5, IL-6, hepatocyte growth factor, leukemia inhibitory factor (LIF), bone morphogenetic protein 2 and also the hormone leptin. STAT3 regulates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis (5). The downregulation of STAT3 in resveratrol-treated medulloblastoma cells confirmed the growth inhibition effects of this drug (6).…”

Kinetics and Signal Activation Properties of Circulating Factor(s) From Healthy Volunteers Undergoing Remote Ischemic Pre-Conditioning

“…Although not significant, the trend for an activation of STAT5 is noteworthy because STAT5 is the only signaling protein, which has so far been demonstrated to be activated by RIPC in human tissue (44). The activation of STAT3 points to members of the cytokine and/or the growth hormone family as potential circulating RIPC transfer factor(s), as both cytokines and growth hormones classically activate the STAT3 and also the STAT5 pathway 29, 45, 46. We did not investigate the signal transduction downstream of STAT3 activation.…”

Cardiac-Specific Deletion of SOCS-3 Prevents Development of Left Ventricular Remodeling After Acute Myocardial Infarction

“…These cytokines activate the janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways, which have protective roles in the development of LV remodeling after AMI (12)(13)(14)(15)(16). Although JAK-STAT-activating cytokines prevent LV remodeling after AMI in animals, little is known about the role of a negative feedback regulator for the JAK-STAT signaling pathway in this process.…”