STAT3 Suppresses Cardiomyocytes Apoptosis in CVB3-Induced Myocarditis Via Survivin

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Viral myocarditis (VMC) is a significant inflammatory cardiovascular disease affecting children and adolescents.
• The precise mechanisms underlying VMC remain unclear, with apoptosis playing a critical role in Coxsackievirus B3 (CVB3)-induced myocarditis.
• Targeting apoptosis presents a potential therapeutic avenue for VMC.

Purpose of the Study:

• To investigate the protective role of Signal transducer and activator of transcription 3 (STAT3) in cardiomyocyte apoptosis during VMC.
• To elucidate the underlying molecular mechanisms of STAT3's protective function in VMC.

Main Methods:

• Establishment of animal and cell models for VMC.
• Utilized AG490, a STAT3 inhibitor, to assess the impact of STAT3 inhibition on VMC severity.
• Employed lentivirus to manipulate STAT3 expression in neonatal mouse cardiomyocytes (NMCs).
• Investigated the role of survivin using the survivin inhibitor YM155.

Main Results:

• STAT3 was found to be significantly activated in VMC models.
• Inhibition of STAT3 (using AG490) exacerbated VMC, leading to increased inflammation, impaired cardiac function, and higher mortality.
• Upregulation of STAT3 attenuated cardiomyocyte apoptosis, while downregulation aggravated it, confirming STAT3's anti-apoptotic role.
• The anti-apoptotic effect of STAT3 was dependent on survivin, as inhibition of survivin abolished STAT3's protective function.

Conclusions:

• STAT3 plays a crucial protective role in CVB3-induced myocarditis.
• STAT3 alleviates cardiomyocyte apoptosis in VMC by targeting survivin.
• Targeting the STAT3-survivin pathway may represent a novel therapeutic strategy for VMC.