GLUT-1/PKM2 loop dysregulation in patients with non-ST-segment elevation myocardial infarction promotes...

Area of Science:

• Immunometabolism
• Molecular biology
• Cardiovascular research

Background:

• Immune cell function is metabolically regulated, with inflammation increasing glucose utilization.
• Understanding glucose metabolism's role in adaptive immunity is crucial for inflammatory diseases.
• Non-ST-segment elevation myocardial infarction (NSTEMI) involves immune dysregulation and inflammation.

Purpose of the Study:

• To investigate the role of glucose metabolism players, glucose transporter 1 (GLUT-1) and pyruvate kinase isozyme M2 (PKM2), in NSTEMI-related immune dysregulation and inflammation.
• To determine if targeting the GLUT-1/PKM2 pathway can modulate inflammation in NSTEMI patients.

Main Methods:

• Comparative analysis of T cell glucose uptake, GLUT-1 expression, and PKM2 localization in NSTEMI patients, chronic coronary syndrome (CCS) patients, and healthy subjects (HSs).
• Assessment of PKM2's subcellular localization (nuclear vs. cytoplasmic) in T lymphocytes.
• In vivo intervention using Shikonin (PKM2 inhibitor) and Fasentin (GLUT-1 inhibitor) in NSTEMI patients to evaluate effects on GLUT-1 expression and pro-inflammatory cytokines.

Main Results:

• NSTEMI patients exhibited significantly higher GLUT-1 expression and glucose uptake in T cells compared to CCS patients and HSs.
• PKM2 showed prevalent nuclear localization in T lymphocytes of NSTEMI patients, unlike CCS and HS groups where it was equally distributed.
• Inhibition of PKM2 and GLUT-1 in NSTEMI patients led to reduced GLUT-1 expression and down-regulated pro-inflammatory cytokine production.

Conclusions:

• NSTEMI patients display a dysregulated GLUT-1/PKM2 metabolic loop, characterized by PKM2 nuclear translocation, which promotes pro-inflammatory gene expression.
• This aberrant metabolic pathway represents a potential novel therapeutic target for NSTEMI management.
• Targeting the GLUT-1/PKM2 axis offers a promising strategy for personalized medicine in NSTEMI.