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STAT3 and cardiac remodeling

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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.

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Abbreviations

AngII:

Angiotensin II

CT-1:

Cardiotrophin-1

DOX:

Doxorubicin

ERK:

Extracellular signal-regulated kinase

ES cell:

Embryonic stem cell

gp130:

Glycoprotein-130

IL:

Interleukin

JAK:

Janus kinase

LIF:

Leukaemia inhibitory factor

MAPK:

Mitogen-activated protein kinase

MHC:

Myosin heavy chain

NF-kB:

Nuclear factor-kB

OSM:

Oncostatin M

PI3K:

Phosphatidylinositol-3-kinase

PPCM:

Peripartum cardiomyopathy

SHP2:

SH2 domain-containing cytoplasmic protein tyrosine phosphatase

sIL-6R:

Soluble IL-6 receptor

sgp130:

Soluble receptor gp130

SOCS:

Suppressor of cytokine signaling

STAT:

Signal transducer and activator of transcription

TNF-α:

Tumor necrosis factor-α

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Authors and Affiliations

  1. Department of Cardiology and Angiology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Arash Haghikia, Britta Stapel, Melanie Hoch & Denise Hilfiker-Kleiner

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  1. Arash Haghikia
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  2. Britta Stapel
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  3. Melanie Hoch
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  4. Denise Hilfiker-Kleiner
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Correspondence to Denise Hilfiker-Kleiner.

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We wish to dedicate this review to Prof H. Drexler.

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Haghikia, A., Stapel, B., Hoch, M. et al. STAT3 and cardiac remodeling. Heart Fail Rev 16, 35–47 (2011). https://doi.org/10.1007/s10741-010-9170-x

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