The Egr-1/miR-15a-5p/GPX4 axis regulates ferroptosis in acute myocardial infarction

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Pathology

Background:

• Acute myocardial infarction (AMI) poses a significant threat to human health.
• The precise molecular mechanisms underlying AMI progression remain incompletely understood.
• Identifying novel therapeutic targets is crucial for managing AMI.

Purpose of the Study:

• To investigate the role of microRNA-15a-5p (miR-15a-5p) in the pathogenesis of AMI.
• To elucidate the molecular pathway involving miR-15a-5p in myocardial cells under hypoxic conditions.
• To identify potential therapeutic strategies targeting the identified pathway.

Main Methods:

• Detection of miR-15a-5p levels in AMI models.
• In vitro studies using hypoxic myocardial cells with miR-15a-5p knockdown.
• Luciferase reporter assays to confirm the direct targeting of glutathione peroxidase 4 (GPX4) by miR-15a-5p.
• Over-expression studies of miR-15a-5p and silencing of early growth response-1 (Egr-1).

Main Results:

• miR-15a-5p was found to be significantly up-regulated in AMI.
• Knockdown of miR-15a-5p reduced mortality in hypoxic myocardial cells.
• GPX4 was identified as a direct target of miR-15a-5p.
• Over-expression of miR-15a-5p exacerbated ferroptosis and myocardial injury.
• Silencing Egr-1 decreased miR-15a-5p, increased GPX4, reduced ferroptosis, and alleviated myocardial injury.

Conclusions:

• The study reveals a novel signaling pathway, Egr-1/miR-15a-5p/GPX4/ferroptosis, implicated in AMI progression.
• miR-15a-5p acts as a key mediator, promoting ferroptosis and aggravating myocardial injury.
• Targeting this pathway, particularly miR-15a-5p or Egr-1, may offer a therapeutic approach for AMI.