GPX3 Overexpression Ameliorates Cardiac Injury Post Myocardial Infarction Through Activating LSD1/Hif1α Axis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Biochemistry

Background:

• Myocardial infarction (MI) leads to cardiomyocyte loss, adverse ventricular remodeling, and heart failure.
• Promoting cardiomyocyte (CM) survival during acute MI is critical for cardiac repair.
• The role of Glutathione Peroxidase 3 (GPX3) in cardiac repair post-MI requires investigation.

Purpose of the Study:

• To investigate the potential role of GPX3 in cardiac repair following MI.
• To elucidate the molecular mechanisms underlying GPX3's effects on CMs during ischemia.

Main Methods:

• Assessed plasma GPX3 levels in acute MI patients and myocardial GPX3 expression in a mouse MI model.
• Utilized cardiomyocyte-specific GPX3 overexpression and knockdown in vitro and in vivo models.
• Employed RNA sequencing, multi-omics analysis, and experimental verification to uncover mechanisms.

Main Results:

• GPX3 expression was significantly upregulated in ischemic myocardium and cardiomyocytes under hypoxia/OGD.
• GPX3 overexpression reduced reactive oxygen species (ROS) and enhanced CM survival in vitro.
• In vivo, GPX3 overexpression attenuated CM apoptosis, reduced myocardial injury, and improved cardiac function post-MI.

Conclusions:

• GPX3 exerts a protective role in ischemic myocardium following MI.
• GPX3's protective effects are mediated, at least partially, through the LSD1/Hif1α pathway.
• GPX3 represents a potential therapeutic target for MI treatment.