MicroRNA-125b Prevents Cardiac Dysfunction in Polymicrobial Sepsis by Targeting TRAF6-Mediated Nuclear Factor κB...

Area of Science:

• Cardiology
• Molecular Biology
• Sepsis Research

Background:

• Sepsis frequently leads to cardiac dysfunction, a major cause of mortality.
• MicroRNAs (miRNAs) play critical roles in regulating cardiac function.
• The specific role of microRNA-125b (miR-125b) in sepsis-induced cardiomyopathy requires further investigation.

Purpose of the Study:

• To investigate the therapeutic effect of increased myocardial miR-125b expression on sepsis-induced cardiac dysfunction.
• To elucidate the molecular mechanisms underlying miR-125b's protective effects in sepsis.

Main Methods:

• Mice hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) prior to inducing sepsis via cecal ligation and puncture (CLP).
• Cardiac function was assessed using echocardiography.
• Survival rates and myocardial inflammatory markers were evaluated.

Main Results:

• LmiR-125b transfection significantly attenuated sepsis-induced cardiac dysfunction, improving fractional shortening and ejection fraction.
• Survival rates were markedly improved in LmiR-125b-treated septic mice.
• miR-125b suppressed ICAM-1 and VCAM-1 expression, reduced inflammatory cell infiltration, and decreased pro-inflammatory cytokines by inhibiting TRAF6-mediated NF-κB activation.
• Myocardial apoptosis was reduced by downregulating p53, Bax, and Bak1 expression.

Conclusions:

• Elevated myocardial miR-125b expression confers protection against sepsis-induced cardiac dysfunction and enhances survival.
• miR-125b emerges as a promising therapeutic target for managing septic cardiomyopathy.