Asprosin Protects H9C2 Cells From Ferroptosis Following Hypoxia/Reoxygenation by Promoting Mitophagy

Area of Science:

• Cardiovascular Research
• Cellular Biology
• Adipokine Signaling

Background:

• Acute myocardial infarction (AMI) is a major global cause of mortality.
• Reperfusion injury following percutaneous coronary intervention can worsen outcomes in AMI patients.
• The protective role of the adipokine asprosin (ASP) in myocardial injury remains under investigation.

Purpose of the Study:

• To investigate the protective effects of asprosin (ASP) against hypoxia/reoxygenation (H/R) induced injury in myocardial cells.
• To elucidate the underlying mechanisms, including ferroptosis and mitophagy pathways.

Main Methods:

• Gene coexpression network analysis (WGCNA) identified Fibrillin 1 (FBN1)-associated modules.
• H9C2 cells were subjected to H/R and treated with ASP.
• Assessed reactive oxygen species (ROS), cell viability (CCK-8), lactate dehydrogenase (LDH), ferroptosis markers, intracellular iron, mitophagy markers, and mitochondrial membrane potential.

Main Results:

• ASP treatment reduced ROS levels and increased cell viability post H/R.
• ASP inhibited ferroptosis by upregulating glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and reducing intracellular iron.
• ASP promoted mitophagy, evidenced by increased PINK1 expression and stabilized mitochondria, an effect reversed by a mitophagy inhibitor.

Conclusions:

• Asprosin (ASP) demonstrates significant protective effects on myocardial cells against ischemia-reperfusion (I/R) injury.
• ASP inhibits ferroptosis and promotes mitophagy in myocardial cells during I/R.
• The mechanism involves ASP-induced PINK1-associated mitophagy, which suppresses ferroptosis in myocardial cells post-H/R injury.