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

Acute myocardial infarction is a leading cause of death globally. Percutaneous coronary intervention is the primary treatment to restore blood flow to the affected myocardium, but reperfusion can cause myocardial injury, affecting the prognosis of patients with acute myocardial infarction. Asprosin (ASP) is a newly discovered adipokine whose role in myocardial protection requires further research.

The GSE240847 dataset was downloaded from the GEO database, and 511 ferroptosis-related genes were collected from the FerrDb database. Gene coexpression network analysis (WGCNA) was performed to identify coexpression modules associated with Fibrillin 1 (FBN1), followed by enrichment analysis. H9C2 cells were subjected to hypoxia/reoxygenation (H/R) and pretreated with ASP at different concentrations. The effects of ASP were determined by measuring cellular reactive oxygen species (ROS), Cell Counting Kit-8 (CCK-8), and lactate dehydrogenase (LDH) levels and assessing the expression of ferroptosis-related proteins, intracellular iron content, mitophagy-related proteins, and mitochondrial membrane potential.

Enrichment analysis showed Gene Ontology (GO) terms linked to GTPase signaling, chromosome behavior, and cell stability. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted mitophagy and MAPK pathways in the FBN1 module. ASP cut ROS, boosted cell viability, and raised glutathione peroxidase 4 (GPX4)/solute carrier family 7 member 11 (SLC7A11) expression, upregulating glutathione and lowering iron particles dose dependently post H/R. It also increased PINK1 and stabilized mitochondria. A mitophagy inhibitor reduced these effects.

This study confirms the protective effects of ASP on myocardial cells after H/R injury and demonstrates that ASP can inhibit ferroptosis and promote mitophagy in myocardial cells during ischemia-reperfusion injury. The potential mechanism may involve ASP promoting PINK1-associated mitophagy in myocardial cells after H/R injury to inhibit ferroptosis.