MicroRNA-27b alleviates septic cardiomyopathy by targeting the Mff/MAVS axis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Mitochondrial Biology

Background:

• Septic cardiomyopathy (SCM) is a severe complication of sepsis, characterized by cardiac dysfunction and myocardial injury.
• Mitochondrial dysfunction plays a critical role in the pathogenesis of SCM.
• The role of microRNAs in regulating mitochondrial dynamics and inflammation in SCM remains incompletely understood.

Purpose of the Study:

• To investigate the protective role of microRNA-27b (miR-27b) in septic cardiomyopathy (SCM).
• To elucidate the regulatory mechanism of miR-27b on the mitochondrial fission factor (Mff)/mitochondrial antiviral signaling protein (MAVS) axis in SCM.

Main Methods:

• Analysis of transcriptome data from septic patient cardiac tissues (GSE79962).
• Measurement of serum miR-27b levels in SCM patients, sepsis patients, and healthy controls.
• Establishment of mouse SCM and HL-1 cardiomyocyte models induced by lipopolysaccharide (LPS).
• Investigation of molecular mechanisms using miR-27b modulators and Mff intervention, coupled with RT-qPCR, Western blot, immunofluorescence, and electron microscopy.

Main Results:

• Downregulation of miR-27b was observed in SCM cardiac tissues and serum.
• LPS-induced SCM models exhibited cardiac dysfunction, myocardial injury, and mitochondrial abnormalities.
• miR-27b targeted Mff, maintaining mitochondrial homeostasis and attenuating LPS-induced inflammation and apoptosis; Mff overexpression reversed these effects.

Conclusions:

• miR-27b alleviates myocardial injury and inflammation in SCM by targeting the Mff/MAVS axis.
• Maintaining mitochondrial homeostasis via miR-27b offers a potential therapeutic strategy for SCM.
• miR-27b represents a promising novel therapeutic target for SCM.