C-Myc Inhibition Using 10058-F4 Suppressed Ischemia Reperfusion Induced Cardiac Microvascular Endothelial Cell...

Area of Science:

• Cardiovascular Biology
• Cellular Mechanisms of Injury
• Molecular Cardiology

Background:

• Myocardial ischemia reperfusion injury (MIRI) research primarily focuses on cardiomyocytes, neglecting microvascular injury.
• Limited strategies exist to mitigate microvascular ischemia reperfusion (I/R) injury.
• The roles of c-Myc and Sam68 in cardiac microvascular endothelial cell (CMEC) pyroptosis are unexplored.

Purpose of the Study:

• To investigate the involvement of c-Myc and Sam68 in pyroptosis of CMECs under I/R conditions.
• To elucidate the regulatory axis governing pyroptosis in CMECs during cardiac I/R.
• To evaluate the therapeutic potential of targeting c-Myc for cardiac I/R injury.

Main Methods:

• Established rat LAD ligation and CMEC hypoxia-reoxygenation (H/R) models.
• Assessed myocardial structure, infarct size, microcirculation, and cardiac function.
• Utilized Western blot and real-time PCR to analyze protein and RNA expression, including c-Myc, Sam68, and NF-κB pathway components.

Main Results:

• c-Myc and Sam68 expression increased in I/R rat hearts and H/R CMECs.
• Inhibition of c-Myc suppressed H/R-induced pyroptosis in CMECs via the Sam68/NF-κB pathway.
• In vivo, c-Myc inhibition attenuated cardiac I/R injury and improved microvascular perfusion.

Conclusions:

• Identified a novel c-Myc/Sam68/NF-κB/pyroptosis regulatory axis in CMECs under I/R stress.
• Targeting this axis protects endothelial function and may enhance reperfusion therapy efficacy.
• This pathway represents a promising therapeutic target for mitigating cardiac microvascular injury.