Single-Cell Transcriptomics of Human Acute Myocardial Infarction Reveals Oxidative Stress-Associated Cardiomyocyte...

Area of Science:

• Cardiovascular Biology
• Cellular Stress Response
• Single-cell Genomics

Background:

• Acute myocardial infarction (AMI) triggers pathological ventricular remodeling due to excessive oxidative stress.
• Adaptive mechanisms within cardiomyocytes responding to oxidative stress remain poorly understood.

Purpose of the Study:

• To delineate oxidative stress heterogeneity in human cardiomyocytes post-AMI.
• To identify adaptive cellular states and potential diagnostic markers.

Main Methods:

• Analysis of 64,510 human cardiomyocytes from five integrated single-cell datasets.
• Stratification into subpopulations based on a composite oxidative stress score (HOX, DTOX, LOX).
• Machine-learning framework and independent cohort validation to identify marker genes.

Main Results:

• A paradoxical finding: high oxidative stress (HOX) cardiomyocytes exhibited greater cellular plasticity.
• HOX cells displayed a unique 'metabolic activation-immune suppression' signature and acted as a communication hub.
• Five core marker genes (TRIM63, ETFDH, TXNIP, CKMT2, PDK4) were identified with stable diagnostic capability for AMI (AUCs 0.688-0.721).

Conclusions:

• Reveals a previously unrecognized adaptive state in post-infarction cardiomyocytes.
• Identified HOX cells as a key subpopulation with distinct functional characteristics.
• The identified marker genes offer promising targets for precision diagnosis and therapeutic intervention in AMI.