Abstract
Nuclear, mitochondrial and cytoplasmic signal transducer and activator of transcription 3 (STAT3) regulates many cellular processes, e.g., the transcription or opening of mitochondrial permeability transition pore, and its activity depends on the phosphorylation of Tyr705 and/or Ser727 sites. In the heterogeneous network of cardiac cells, STAT3 promotes cardiac muscle differentiation, vascular element formation and extracellular matrix homeostasis. Overwhelming evidence suggests that STAT3 is beneficial for the heart, plays a role in the prevention of age-related and postpartum heart failure, protects the heart against cardiotoxic doxorubicin or ischaemia/reperfusion injury, and is involved in many cardioprotective strategies (e.g., ischaemic preconditioning, perconditioning, postconditioning, remote or pharmacological conditioning). Ischaemic heart disease is still the leading cause of death worldwide, and many cardiovascular risk factors contribute to the development of the disease. This review focuses on the effects of various cardiovascular risk factors (diabetes, aging, obesity, smoking, alcohol, depression, gender, comedications) on cardiac STAT3 under non-ischaemic baseline conditions, and in settings of ischaemia/reperfusion injury with or without cardioprotective strategies.
Highlights
Signal transducer and activator of transcription 3 (STAT3) has a central role in transmitting extracellular signals from the plasma membrane to the nucleus and mitochondria, where it influences transcription and mitochondrial function, thereby regulating diverse biological processes.1.1
This review focuses on the effects of various cardiovascular risk factors on cardiac signal transducer and activator of transcription 3 (STAT3), a well-known cardioprotective signal molecule, under non-ischaemic baseline conditions and in settings of ischaemia/reperfusion injury with or without cardioprotective strategies
The activation of the leptin-STAT3 signalling by high-fat diet was reported to be associated with hypertrophy and increased expression and activation of cardiac STAT3 in C57BL/6 mice, while STAT3 activation remained unchanged in leptin-receptor-deficient db/db mice [51,52] (Table 3)
Summary
Signal transducer and activator of transcription 3 (STAT3) has a central role in transmitting extracellular signals from the plasma membrane to the nucleus and mitochondria, where it influences transcription and mitochondrial function, thereby regulating diverse biological processes
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